Total Syntheses of Carazostatin, Hyellazule, and Carbazoquinocins B-F

Article abstract of DOI:10.1021/jo962038t

Total syntheses of carazostatin (1), hyellazole (2a), and carbazoquinocins B-F (3b-f) have been completed. The cross-coupling reaction between 3-iodoindole 8 and vinylstannane 11b gave the 3-alkenylindole 7. Treatment of 7 with ethynylmagnesium bromide, followed by etherification of the resulting alcohol 12 with MOMCl, yielded the 3-alkenyl-2-propargylindole 6. The compound 6 was treated with t-BuOK in t-BuOH at 90°C to obtain the desired carbazoles 4 together with the N-deprotected carbazole 13 through an allene-mediated electrocyclic reaction. The carbazole 13a, derived from 4a or 4c, was converted into the triflate 24 in two steps. The triflate 24 was subjected to the Suzuki cross-coupling reaction with either 9-heptyl-9-BBN or phenylboronic acid in the presence of a palladium catalyst to produce the 1-heptylcarbazole 25a and the 1-phenylcarbazole 25b. Cleavage of the ether bond of 25a yielded carazostatin (1). Cleavage of the ether bond of 25b followed by O-methylation gave hyellazole (2a). Oxidation of carazostatin (1) with benzene seleninic anhydride afforded carbazoquinocin C (3c). In a similar way, carbazoquinocins B and D-F (3b,d-f) were synthesized, respectively.

Full text of DOI:10.1021/jo962038t

J . Org. Chem. 1997, 62, 2535-2543
2535
Tota l Syn th eses of Ca r a zosta tin , Hyella zole, a n d
Ca r ba zoqu in ocin s B-F
Tominari Choshi, Takuya Sada, Hiroyuki Fujimoto, Chizu Nagayama, Eiichi Sugino, and
Satoshi Hibino*
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University,
Fukuyama, Hiroshima 729-02, J apan
Received October 31, 1996X
Total syntheses of carazostatin (1), hyellazole (2a ), and carbazoquinocins B-F (3b-f) have been
completed. The cross-coupling reaction between 3-iodoindole 8 and vinylstannane 11b gave the
3-alkenylindole 7. Treatment of 7 with ethynylmagnesium bromide, followed by etherification of
the resulting alcohol 12 with MOMCl, yielded the 3-alkenyl-2-propargylindole 6. The compound 6
was treated with t-BuOK in t-BuOH at 90 °C to obtain the desired carbazoles 4 together with the
N-deprotected carbazole 13 through an allene-mediated electrocyclic reaction. The carbazole 13a ,
derived from 4a or 4c, was converted into the triflate 24 in two steps. The triflate 24 was subjected
to the Suzuki cross-coupling reaction with either 9-heptyl-9-BBN or phenylboronic acid in the
presence of a palladium catalyst to produce the 1-heptylcarbazole 25a and the 1-phenylcarbazole
25b. Cleavage of the ether bond of 25a yielded carazostatin (1). Cleavage of the ether bond of
25b followed by O-methylation gave hyellazole (2a ). Oxidation of carazostatin (1) with benzene
seleninic anhydride afforded carbazoquinocin C (3c). In a similar way, carbazoquinocins B and
D-F (3b,d -f) were synthesized, respectively.
Since 1979, new highly substituted carbazole alkaloids
have been found by several groups in different terrestrial
plants.1 Hyellazoles (2) were isolated from blue-green
algae Hyella caespitosa by Moore, representing the first
carbazole alkaloids of marine origin.2,3 Carazostatin (1),
a free radical scavenger, was isolated from Streptomyces
chromofuscus by Kato in 1989.4,5 Carbazoquinocins A-F
(3), found in Streptomyces violaceus 2448-SVT2 by Seto
in 1995, have the o-quinone structure and possess anti-
oxidation properties.6,7 These novel alkaloids attracted
considerable interest among synthetic organic chemists
because of their potent biological activities.8
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) For reviews, see: (a) Husson, H.-P. In The Alkaloids; Brossi, A.,
Ed.; Academic Press: New York, 1985; Vol. 26, pp 1-51. (b) Bhatta-
charyya, P.; Chakraborty, D. P. In Progress in Chemical and Organic
Natural Products; Herz, W., Grisebach, H., Kirby, G. W., Tamm, C.,
Eds.; Springer Verlag: Wien, 1987; Vol. 52, pp 159-209. (c)
Chakraborty, D. P.; Roy, S. In Progress in Chemical and Organic
Natural Products; Herz, W., Grisebach, H., Kirby, G. W., Tamm, C.,
Eds.; Springer Verlag: Wien, 1991; Vol. 57, pp 71-152. (d) Chakraborty,
D. P. In The Alkaloids; Brossi, A., Ed.; Academic Press: New York,
1993; Vol. 44, pp 257-364.
We are currently interested in the synthesis of het-
eroaromatic compounds containing a nitrogen atom by
thermal electrocyclic reactions9 of either conjugated
hexatriene or monoazahexatriene systems including one
double bond of an aromatic or heteroaromatic portion.8g,10
(2) For the isolation of hyellazoles, see: Cardellina, J . H.; Kirkup,
M. P.; Moore, R. E.; Mynderse, J . S.; Seff, K.; Simmons, C. J .
Tetrahedron Lett. 1979, 4915-4916.
(7) For the previous synthesis of carbazoquinocins A and D, see:
Shin, K.; Ogasawara, K. Synlett 1996, 922-924.
(3) For previous syntheses of hyellazole, see: (a) Kano, S.; Sugino,
E.; Hibino, S. J . Chem. Soc., Chem. Commun. 1980, 1241-1242. (b)
Kano, S.; Sugino, E.; Shibuya, S.; Hibino, S. J . Org. Chem. 1981, 46,
3856-3859. (c) Takano, S.; Suzuki, Y.; Ogasawara, K. Heterocycles
1981, 16, 1479-1480. (d) Kawasaki, T.; Nonaka, Y.; Sakamoto, M. J .
Chem. Soc., Chem. Commun. 1989, 43-44. (e) Moody, C. J .; Shah, P.
J . Chem. Soc., Perkin Trans. 1 1989, 2463-2471. (f) Danheiser, R.
L.; Brisbois, R. G.; Kowalczyk, J . J .; Miller, R. F. J . Am. Chem. Soc.
1990, 112, 3039-3100. (g) Kawasaki, T.; Nonaka, Y.; Akahane, M.;
Maeda, M.; Sakamoto, M. J . Chem. Soc., Perkin Trans. 1 1993, 1777-
1781. (h) Beccalli, E. M.; Marchesini, A.; Pilati, T. J . Chem. Soc.,
Perkin Trans. 1 1994, 579-587. (i) Kno¨lker, H.-J.; Baum, E.; Hopfmann,
T. Tetrahedron Lett. 1995, 36, 5339-5342.
(8) For recent reviews, see: (a) Pindur, U. Chimia 1990, 44, 406-
412. (b) Bergman, J .; Pelcman, B. Pure Appl. Chem. 1990, 62, 1967-
1976. (c) Kno¨lker, H.-J . Synlett 1992, 371-387. (d) Kawasaki, T.;
Sakamoto, M. J . Indian Chem. Soc. 1994, 71, 443-457. (e) Moody, C.
J . Synlett 1994, 681-688. (f) Kno¨lker, H.-J . In Advances in Nitrogen
Heterocycles; Moody, C. J ., Ed.; J AI Press: Greenwich, CT, 1995; Vol.
1, pp 173-204. (g) Hibino, S.; Sugino, E. In Advances in Nitrogen
Heterocycles; Moody, C. J ., Ed.; J AI Press: Greenwich, CT, 1995; Vol.
1, pp 205-227.
(9) (a) Woodward, R. B.; Hoffmann, R. J . Am. Chem. Soc. 1965, 87,
395-397. (b) Woodward, R. B.; Hoffmann, R. The Conservative of
Orbital Symmetry; Verlag Chemie: Weinheim, 1970; Chapter 5. (c)
Fleming, I. Fontier Orbital and Organic Chemistry; Wiley: London,
1976. (d) Marvel, E. N. Thermal Electrocyclic Reactions; Academic
Press: New York, 1980; Chapter 2. (e) Okamura, W. H.; de Lera, A.
R. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Paquette, L. A., Eds.; Pergamon Press: New York, 1991; Vol. 5, pp
699-750.
(4) For the isolation of carazostatin, see: Kato, S.; Kawai, H.;
Kawasaki, T.; Toda, Y.; Urata, T.; Hayakawa, Y. J . Antibiot. 1989,
42, 1879-1881.
(5) For previous syntheses of carazostatin, see: (a) J ackson, P. M.;
Moody, C. J . Synlett 1990, 521-522. (b) J ackson, P. M.; Moody, C. J .;
Mortimer, R. J . J . Chem. Soc., Perkin Trans. 1 1991, 2941-2944. (c)
Shin, K.; Ogasawara, K.; Chem. Lett. 1995, 289-290. (d) Kno¨lker, H.-
J .; Hopfmann, T. Synlett 1995, 981-983.
(6) For the isolation of carbazoquinocins A-F, see: Tanaka, M.;
Shin-ya, K.; Furihata, K.; Seto, H. J . Antibiot. 1995, 48, 326-328.
(10) (a) Choshi, T.; Yamada, S.; Sugino, E.; Kuwada, T.; Hibino, S.
J . Org. Chem. 1995, 60, 5899-5904. (b) Yoshioka, H.; Choshi, T.;
Sugino, E.; Hibino, S. Heterocycles 1995, 41, 161-174. (c) Yoshioka,
H.; Matsuya, Y.; Choshi, T.; Sugino, E.; Hibino, S. Chem. Pharm. Bull.
1996, 44, 709-714 and related references cited therein.
S0022-3263(96)02038-5 CCC: $14.00 © 1997 American Chemical Society

2536 J . Org. Chem., Vol. 62, No. 8, 1997
Choshi et al.
Sch em e 1
6b (97% from 7b). On the other hand, 3-iodoindole 10
was converted into the N-MOM-indole 8b in good yield
(96%). Cross-coupling reaction between 8b and the
alkenylstannane 11a (or 11b) in a similar manner gave
the 3-alkenylindoles 7c (89%) and 7d (94%). Treatment
of 7c (or 7d ) with ethynylmagnesium bromide followed
by treatment of the resulting alcohol 12c (or 12d ) with
MOMCl produced the 3-alkenyl-2-propargylindoles 6c
(85% from 7c) and 6d (70% from 7d ).
We next attempted the construction of the trisubsti-
tuted carbazole nucleus by using two types of N-protect-
ing groups of the indole nitrogen atom (Scheme 2). The
3-alkenyl-2-propargylindole 6a was heated at 90 °C in
tert-butyl alcohol in the presence of potassium tert-
butoxide according to the previous reported method13 for
allene generation to yield the expected carbazole 4a (43%)
together with the N-deprotected carbazole 13a (41%). In
a similar way, 2-propargylindole 6b gave the carbazole
4b (20%) and N-deprotected carbazole 13b (57%), respec-
tively. By contrast, heating of the 3-alkenyl-2-propar-
gylindole 6c in tert-butyl alcohol in the presence of
potassium tert-butoxide produced only the N-MOM-
carbazole 4c (92%). Also in the case of the 2-propar-
gylindole 6d , only the N-MOM-carbazole 4d was obtained
(96%). In the former case, it was considered that the
N-benzenesulfonyl group was perhaps removed partly by
potassium tert-butoxide14 during this reaction, but both
protecting groups seemed to be good groups for this
reaction. Fortunately, this benzo annelation proceeded
without elimination of the MOM oxy group.
Investigation of the proposed mechanism is shown in
Scheme 3. 3-Iodoindole 8a was treated with ethynyl-
magnesium bromide to obtain the propargyl alcohol 14
(99%), which was converted into the MOM ether 15
(89%). Treatment of 15 with potassium tert-butoxide in
tert-butyl alcohol at 90 °C for 3 h produced the allenylin-
dole 16 in good yield (79%) with retention of the MOM
ether.15 However, the cross-coupling reaction between
16 and the alkenylstannane 11a (or 11b) failed. Thus,
although it is undeniable that this benzo annelation
proceeds through an ionic process, at present it is
considered to proceed by initial generation of an allene
intermediate which undergoes electrocyclic reaction to
give the trisubstituted carbazole.
In the course of our study to develop a more efficient
strategy for synthesizing these carbazole alkaloids than
the previous synthesis of hyellazoles by the thermal
electrocyclic reaction of the 2,3-bisalkenylindoles,3a,b we
found that these 3-oxygenated carbazole alkaloids have
a methyl group at the 2-position. On the basis of this
finding, we envisaged that an electrocyclic reaction of an
allene intermediate 5, possessing an appropriate func-
tional group in order to introduce an alkyl or aryl group
to the 1-position of carbazole as depicted in retro-
synthetic Scheme 1, might be more reactive without
using an oxidative agent than the reaction of the 2,3-
bisalkenylindole system for producing these alkaloids.
The 3-alkenyl-2-propargylindole 6 was selected as a
precursor of allene intermediate 5. It would be derived
from 3-iodoindole 8 in several steps, and then carbazo-
quinocines 3 would be obtained from carazostatin (1) and
its related compounds. In this paper, we describe total
synthesis of carazostatin (1), hyellazole (2a ), and carba-
zoquinocins B-F (3b-f) together with details of the
preliminary report.11
For the synthesis of the precursor 3-alkenyl-2-propar-
gylindole 6, 3-iodoindole-2-carboxaldehyde (10) (Scheme
2), prepared from 2-formylindole (9) according to the
reported procedure12 as the starting material, was con-
verted into the N-(benzenesulfonyl)indole 8a (83%).
Cross-coupling reaction between 8a and the alkenylstan-
nane 11a (or 11b) in the presence of bis(triphenylphos-
phine)palladium(II) chloride [Pd(PPh3)2Cl2] gave the
3-alkenylindoles 7a (84%) and 7b (67%), respectively.
Treatment of 7a (or 7b) with ethynylmagnesium bromide
followed by treatment of the resulting alcohol 12a (or
12b) with chloromethyl methyl ether (MOMCl) produced
the 3-alkenyl-2-propargylindoles 6a (80% from 7a ) and
Studies to introduce an alkyl group into the 1-position
of carbazole were done with carbazoles 4b and 13b
(Scheme 4). Cleavage of the MOM ether of 4b and 13b
with trimethylsilyl chloride (TMSCl) and sodium iodide
(NaI)16 gave 1-hydroxycarbazoles 17 (94%) and 18 (85%),
respectively. The phenols 17 and 18 were converted into
the triflates 19 (96%) and 20 (98%), which were subjected
to the Suzuki cross-coupling reaction.17 The reaction
between 20 and 9-heptyl-9-borabicyclo[3.3.1]nonane (21)
[prepared from 9-borabicyclo[3.3.1]nonane (9-BBN) and
1-heptene] proceeded in the presence of a palladium
catalyst to yield the 1-heptylcarbazole 22 (53%).
A
(13) Hayakawa, K.; Ohsuki, S.; Kanematsu, K. Tetrahedron Lett.
1986, 27, 4205-4208. (b) Nagashima, S.; Kanematsu, K. Tetrahedron:
Asymmetry 1990, 1, 743-749.
(14) Eissenstat, M. A.; Weaver, J . D., III Tetrahedron Lett. 1995,
36, 2029-2032.
(15) (a) Shuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis;
Wiley: New York, 1984. (b) Elnager, H. Y.; Okamura, W. H. J . Org.
Chem. 1988, 53, 3060-3066. (c) Turnbull, P.; Moore, H. W. J . Org.
Chem. 1995, 60, 3274-3275. (d) Wender, P. A.; J enkins, T. E.; Suzuki,
S. J . Am. Chem. Soc. 1995, 117, 1843-1844. (e) J acobi, P. A.; Kravitz,
T. E.; Zheng, W. J . Org. Chem. 1995, 60, 376-385.
(16) Rigby, J . H.; Wilson, J . Z. Tetrahedron Lett. 1984, 25, 1429-
1432.
(11) (a) Choshi, T.; Sada, T.; Fujimoto, H.; Nagayama, C.; Sugino,
E.; Hibino, S. Tetrahedron Lett. 1996, 37, 2593-2596. (b) Choshi, T.;
Fujimoto, H.; Sugino, E.; Hibino, S. Heterocycles 1996, 43, 1847-1854.
(12) Sakamoto, T.; Nagano, T.; Kondo, Y.; Yamanaka, H. Chem.
Pharm. Bull. 1988, 36, 2248-2252.

Carazostatin, Hyellazole, and Carbazoquinocins
J . Org. Chem., Vol. 62, No. 8, 1997 2537
Sch em e 2
Sch em e 3
Sch em e 4
coupling reaction between 24 and 21 in the presence of
a palladium catalyst gave the 1-heptylcarbazole 25a
(85%), which was treated with boron tribromide (BBr3)
to produce carazostatin (1) (90%). Furthermore, the
cross-coupling reaction between 24 and phenylboronic
acid in the presence of a palladium catalyst also gave the
1-phenylcarbazole 25b (96%), which was treated with
BBr3 followed by O-methylation with methyl iodide3i to
produce hyellazole (2a ) (86% from 25b). The spectro-
scopic data and physical data of carazostatin (1) and
hyellazole (2a ) were virtually identical with those re-
ported for the natural2,4 and synthetic3,5 products. Car-
bazoquinocin C (3c) was readily obtained from carazosta-
tin (1) by using benzeneseleninic anhydride [(PhSeO)2O]18
as the oxidizing agent (95%). Thus, a synthetic route to
similar reaction between 19 and 21 was unsuccessful
because of steric hindrance.
On the basis of this model experiment, the N-protecting
groups of carbazoles 4a ,c were removed to form the
carbazole 13a (98% from 4a and 61% from 4c) for the
synthesis of natural products (Scheme 5). Treatment of
13a with TMSCl and NaI followed by treatment of
trifluoromethanesulfonyl anhydride (Tf2O) and pyridine
gave the triflate 24 (85% from 13a ). Subsequent cross-
(17) (a) Ishiyama, T.; Kizaki, H.; Miyaura, N.; Suzuki, A. Tetrahe-
dron Lett. 1993, 34, 7595-7598. (b) Oh-e, T.; Miyaura, N.; Suzuki, A.
J . Org. Chem. 1993, 58, 2201-2208. (c) Oh-e, T.; Miyaura, N.; Suzuki,
A. Synlett 1990, 221-223. (d) Miyaura, N.; Ishiyama, T.; Hayashi,
H.; Ishikawa, M.; Satoh, M.; Suzuki, A. J . Am. Chem. Soc. 1989, 111,
314-321.

2538 J . Org. Chem., Vol. 62, No. 8, 1997
Choshi et al.
Sch em e 5
Sch em e 6
carbazoquinocins B (3b ), D (3d ), E (3e), and F (3f) is
available.
raphy. Melting points are uncorrected. 1H NMR (60 MHz)
and 13C NMR were taken in CDCl3 with Me4Si as an internal
standard unless otherwise stated. Low- and high-resolution
mass spectra were measured at 70 eV (EI).
Finally, the triflate 24 was subjected to the cross-
coupling reaction with 9-alkyl-9-BBN 27a -d in a similar
manner to give the 1-alkylcarbazoles 28a -d (56-78%).
Subsequent treatment of 28a -d with BBr3 afforded
3-hydroxycarbazoles 29a -d (64-97%), which were oxi-
dized by (PhSeO)2O in the same way to yield carbazo-
quinocins B (3b, 90%), D (3d , 84%), E (3e, 70%), and F
(3f, 92%), respectively (Scheme 6). The spectroscopic
details of synthetic carbazoquinocins B-F (3b-f) were
identical with those reported for natural products.6 Rf
values of synthetic carbazoquinocins B and D were
consistent with those of authentic samples in various
solvent systems. Although the melting points of all
synthetic carbazoquinocins B-F (3b-f) were slightly
higher than those of natural products, exact measure-
ment of melting points is difficult because of dark-colored
substances.
In conclusion, a new benzo annelation method based
on the allene-mediated electrocyclic reaction of 2,3-
functionalized indoles provides an effective route to the
highly-functionalized carbazole ring, as shown for the
total syntheses of carazostatin (1), hyellazole (2a ), and
carbazoquinocins B-F (3b-f). As regards hyellazole,
this key reaction furnished more effective results than
those of our previous synthesis.3a,b Moreover, the first
total syntheses of carbazoquinocins B, C, E, and F
(3b,c,e,f) were demonstrated.
3-Iod oin d ole-2-ca r boxa ld eh yd e (10). An ice-cooled solu-
tion of I2 (1.67 g, 6.6 mmol) in DMF (30 mL) was added to a
solution of 2-formylindole (9) (0.96 g, 6.6 mmol) and powdered
KOH (1.3 g, 23.8 mmol). After stirring at rt for 4 h, the
mixture was poured into a solution of 28% NH4OH (100 mL)
and NaHSO3 (1 g, 9.6 mmol) in water (1.5 L). The precipitates
were separated by filtration to give the 3-iodoindole 10 (1.45
g, 81%): mp 193-194 °C (from EtOH); IR (KBr) 3330, 1653
1
cm-1; H NMR δ 7.08-7.70 (m, 4 H), 9.77 (s, 1 H); MS m/ z
271 (M+). Anal. Calcd for C9H6NOI: C, 39.88; H, 2.23; N,
5.17. Found: C, 40.01; H, 2.33; N, 5.06.
N-(Ben zen esu lfon yl)-3-iod oin d ole-2-ca r b oxa ld eh yd e
(8a ). An ice-cooled solution of 3-iodoindole 10 (500 mg, 1.84
mmol) in DMF (15 mL) was added to a suspension of 60% NaH
(89 mg, 2.21 mmol) in DMF (5 mL). After stirring at the same
temperature for 30 min, a solution of benzenesulfonyl chloride
(0.28 mL, 2.21 mmol) was added to the above mixture. The
reaction mixture was stirred at the same temperature for 2 h
and then treated with water (30 mL). The mixture was
extracted with EtOAc. The EtOAc layer was washed with
water and brine and dried over Na2SO4. The solvent was
removed, and the residue was purified by column chromatog-
raphy (silica gel, 30 g) using EtOAc-hexane (3:7, v/v) as an
eluent to give the N-(benzenesulfonyl)indole 8a (632 mg,
83%): mp 189.5-191 °C (from EtOAc); IR (KBr) 1688, 1368
1
cm-1; H NMR δ 7.15-8.31 (m, 9 H), 10.33 (s, 1 H); MS m/ z
411 (M+). Anal. Calcd for C15H10NO3IS: C, 43.81; H, 2.45;
N, 3.41. Found: C, 43.92; H, 2.55; N, 3.40.
3-Iod o-N-(m et h oxym et h yl)in d ole-2-ca r b oxa ld eh yd e
(8b). An ice-cooled solution of 3-iodoindole 10 (1.45 g, 5.3
mmol) in DMF (20 mL) was added to a suspension of 60% NaH
(276 mg, 6.9 mmol) in DMF (10 mL). After stirring at rt for
30 min, a solution of MOMCl (1.6 mL, 21.4 mmol) was added
to the above mixture. The reaction mixture was stirred at rt
for 12 h and then poured into ice water. The mixture was
extracted with EtOAc. The EtOAc layer was washed with
water and brine and dried over Na2SO4. The solvent was
removed, and the residue was purified by column chromatog-
raphy (silica gel, 50 g) using EtOAc-hexane (1:9, v/v) as an
eluent to give the N-MOM-indole 8b (1.58 g, 94%): mp 81-
Exp er im en ta l Section
Gen er a l. Most reactions were conducted in flame-dried
glassware under argon atmosphere. All air-sensitive reactions
were run under argon atmosphere. THF was freshly distilled
from sodium benzophenone ketyl. DMF was freshly distilled
under reduced pressure after drying over CaH2. Silica gel (60-
100 mesh, Merck Art 7734) was used for column chromatog-
(18) Barton, D. H. R.; Brewster, A. G.; Ley, S. V.; Read, C. M.;
Rosenfeld, M. N. J . Chem. Soc., Perkin Trans. 1 1981, 1473-1476.

Carazostatin, Hyellazole, and Carbazoquinocins
J . Org. Chem., Vol. 62, No. 8, 1997 2539
1
83.5 °C (from EtOAc); IR (KBr) 1611 cm-1; 1H NMR δ 3.26 (s,
3 H), 5.88 (s, 2 H), 7.02-7.58 (m, 4 H), 9.92 (s, 1 H); MS m/ z
315 (M+). Anal. Calcd for C11H10NO2I: C, 41.93; H, 3.20; N,
4.45. Found: C, 42.05; H, 3.31; N, 4.40.
P a lla d iu m -Ca ta lyzed Cr oss-Cou p lin g Rea ction be-
tw een th e 3-Iod oin d ole 8 a n d th e Alk en yltr i-n -bu tyltin
11. A typical example of 7a is represented as follows, and
other examples of 7b-d show the compound name, yield, and
physical data.
cm-1; H NMR δ 2.63 (d, 1 H, J ) 2 Hz), 4.29 (d, 1 H, J ) 10
Hz, exchangeable with D2O), 5.60 (dd, 1 H, J ) 2, 10 Hz), 5.73
(dd, 1 H, J ) 2, 16 Hz), 6.17 (dd, 1 H, J ) 2, 10 Hz), 6.94 (dd,
1 H, J ) 10, 16 Hz), 7.02-8.18 (m, 9 H); MS m/ z 337 (M+).
HRMS Calcd for C21H19NO4S: 337.0772. Found: 337.0790.
3-(Eth oxyeth en yl)-2-(1-h ydr oxypr op-2-yn -1-yl)-N-(m eth -
oxym eth yl)in d ole (12c). The same procedure as above was
carried out by using 7c (89%): oil; IR (neat) 3432, 3282 cm-1
;
1H NMR δ 1.31 (t, 3 H, J ) 7 Hz), 2.56 (d, 1 H, J ) 2 Hz), 3.19
(s, 3 H), 3.88 (q, 2 H, J ) 7 Hz), 4.17 (d, 1 H, J ) 2 Hz), 5.45
(d, 1 H, J ) 10 Hz), 5.89 (d, 1 H, J ) 12 Hz), 5.77-5.92 (m, 1
H), 6.06 (d, 1 H, J ) 10 Hz), 6.79 (d, 1 H, J ) 12 Hz), 7.07-
N-(Ben zen esu lfon yl)-3-(2-eth oxyeth en yl)in d ole-2-ca r -
boxa ld eh yd e (7a ). A solution of (2-ethoxyethenyl)tri-n-
butyltin (11a ) (818 mg, 2.27 mmol) was added to a suspension
of 3-iodoindole 8a (620 mg, 1.51 mmol), Et4N+Cl- (250 mg,
1.51 mmol), and Pd(PPh3)2Cl2 (53 mg, 0.076 mmol) in DMF (5
mL). After stirring at 80 °C for 2 h, the reaction mixture was
treated with 30% aqueous KF solution at rt. The mixture was
stirred for 30 min and then filtered with Celite. The filtrate
was extracted with EtOAc. The EtOAc layer was washed with
water and brine and dried over Na2SO4. The organic layer
was removed, and the residue was purified by column chro-
matography (silica gel, 30 g) using EtOAc-hexane (1:9, v/v)
as an eluent to give the 3-(ethoxyethenyl)indole 7a (448 mg,
84%): mp 122-124 °C (from EtOAc); IR (KBr) 1668, 1368
7.71 (m, 4 H); MS m/ z 285 (M+). HRMS Calcd for C17H19
-
NO3: 285.1364. Found: 285.1345.
3-Eth en yl-2-(1-h yd r oxyp r op -2-yn -1-yl)-N-(m eth oxym -
eth yl)in d ole (12d ). The same procedure as above was carried
out by using 7d (94%): oil; IR (neat) 3283, 2116 cm-1; 1H NMR
δ 2.53 (d, 1 H, J ) 2 Hz), 3.18 (s, 3 H), 4.16 (d, 1 H, J ) 8 Hz),
5.29 (dd, 2 H, J ) 2, 11 Hz), 5.42 (d, 1 H, J ) 10 Hz), 5.61 (dd,
1 H, J ) 2, 16 Hz), 5.76 (dd, 1 H, J ) 2, 8 Hz), 6.01 (d, 1 H, J
) 10 Hz), 6.82 (dd, 1 H, J ) 11, 16 Hz), 6.99-7.89 (m, 4 H);
MS m/ z 241 (M+). HRMS Calcd for C15H15NO2: 241.1102.
Found: 241.1099.
1
cm-1; H NMR δ 1.36 (t, 3 H, J ) 7 Hz), 3.97 (q, 2 H, J ) 7
P r ep a r a tion of th e O-MOM Eth er 6. A typical example
of 6a is represented as follows, and other examples of 6b-d
show the compound name, yield, and physical data.
Hz), 6.45 (d, 1 H, J ) 14 Hz), 7.21-7.78 (m, 3 H), 7.53 (d, 1 H,
J ) 14 Hz), 8.07-8.32 (m, 6 H), 10.48 (s, 1 H); MS m/ z 355
(M+). Anal. Calcd for C19H17NO4S: C, 64.21; H, 4.82; N, 3.94.
Found: C, 64.23; H, 5.00; N, 3.89.
N-(Ben zen esu lfon yl)-3-(2-eth oxyeth en yl)-2-[1-[(m eth -
oxym eth yl)oxy]p r op -2-yn -1-yl]in d ole (6a ). A solution of
MOMCl (0.36 mL, 4.72 mmol) was added to a solution of
propargyl alcohol 12a (360 mg, 0.94 mmol) and i-Pr2NEt (0.98
mL, 5.64 mmol) in CH2Cl2 (15 mL). The solution was stirred
at 50 °C for 12 h, cooled to rt, and treated with water. The
mixture was extracted with CH2Cl2. The CH2Cl2 layer was
washed with brine, dried over Na2SO4, and concentrated. The
residue was purified by column chromatography (silica gel, 20
g) using EtOAc-hexane (3:17, v/v) as an eluent to give the
MOM ether 6a (395 mg, 97%) as an oil: IR (neat) 3288, 2116,
N-(Ben zen esu lfon yl)-3-et h en ylin d ole-2-ca r b oxa ld e-
h yd e (7b). A similar cross-coupling reaction between 8a and
11b was carried out as above to give the 3-ethenylindole 7b
(67%): mp 152.5-154 °C (from EtOAc); IR (KBr) 1676, 1367
cm-1; 1H NMR δ 5.71 (dd, 1 H, J ) 2, 12 Hz), 5.93 (dd, 1 H, J
) 2, 18 Hz), 7.25 (dd, 1 H, J ) 12, 18 Hz), 7.28-8.31 (m, 9 H),
10.52 (s, 1 H); MS m/ z 311 (M+). Anal. Calcd for C17H13
-
NO3S: C, 65.58; H, 4.21; N, 4.50. Found: C, 65.63; H, 4.25;
N, 4.61.
3-(2-Eth oxyeth en yl)-N-(m eth oxym eth yl)in d ole-2-ca r -
boxa ld eh yd e (7c). A similar cross-coupling reaction between
8b and 11a was carried out as above to give the 3-(ethoxy-
1373 cm-1; H NMR δ 1.34 (t, 3 H, J ) 7 Hz), 2.60 (d, 1 H, J
1
) 3 Hz), 3.40 (s, 3 H), 3.92 (q, 2 H, J ) 7 Hz), 4.63 (d, 1 H, J
) 7 Hz), 4.95 (d, 1 H, J ) 7 Hz), 6.17 (d, 1 H, J ) 13 Hz), 6.55
(d, 1 H, J ) 3 Hz), 7.07 (d, 1 H, J ) 13 Hz), 7.09-8.28 (m, 9
H); MS m/ z 425 (M+). HRMS Calcd for C23H23NO5S: 425.1296.
Found: 425.1305.
1
ethenyl)indole 7c (89%): oil; IR (KBr) 1611 cm-1; H NMR δ
1.42 (t, 3 H, J ) 7 Hz), 3.30 (s, 3 H), 4.02 (q, 2 H, J ) 7 Hz),
5.91 (s, 2 H), 6.23 (d, 1 H, J ) 12 Hz), 6.99 (d, 1 H, J ) 12 Hz),
7.09-7.79 (m, 4 H), 10.02 (s, 1 H); MS m/ z 259 (M+). HRMS
Calcd for C15H17NO3: 259.1208. Found: 259.1191.
N-(Ben zen esu lfon yl)-3-eth en yl-2-[1-[(m eth oxym eth yl)-
oxy]p r op -2-yn -1-yl]in d ole (6b). The same procedure as
above was carried out by using 12b to give the MOM ether
6b (98%): oil; IR (neat) 3300, 2128, 1375 cm-1; 1H NMR δ 2.60
(d, 1 H, J ) 2 Hz), 3.39 (s, 3 H), 4.62 (d, 1 H, J ) 7 Hz), 4.94
(d, 1 H, J ) 7 Hz), 5.45 (dd, 1 H, J ) 2, 12 Hz), 5.75 (dd, 1 H,
J ) 2, 18 Hz), 6.60 (d, 1 H, J ) 2 Hz), 7.25 (dd, 1 H, J ) 12,
18 Hz), 7.18-8.27 (m, 9 H); MS m/ z 381 (M+). HRMS Calcd
for C21H19NO4S: 381.1034. Found: 381.1033.
3-(Eth oxyeth en yl)-N-(m eth oxym eth yl)-2-[1-[(m eth oxym -
eth yl)oxy]p r op -2-yn -1-yl]in d ole (6c). The same procedure
as above was carried out by using 12c to give the MOM ether
6c (95%): oil; IR (neat) 3273, 2114 cm-1; 1H NMR δ 1.29 (t, 3
H, J ) 7 Hz), 2.53 (d, 1 H, J ) 2 Hz), 3.21 (s, 3 H), 3.29 (s, 3
H), 3.82 (q, 2 H, J ) 7 Hz), 4.44 (d, 1 H, J ) 6 Hz), 4.74 (d, 1
H, J ) 6 Hz), 5.57 (s, 2 H), 5.79 (d, 1 H, J ) 2 Hz), 5.88 (d, 1
H, J ) 12 Hz), 6.71 (d, 1 H, J ) 12 Hz), 6.83-7.51 (m, 4 H);
MS m/ z 329 (M+). HRMS Calcd for C19H23NO4: 329.1626.
Found: 329.1641.
3-Eth en yl-N-(m eth oxym eth yl)-2-[1-[(m eth oxym eth yl)-
oxy]p r op -2-yn -1-yl]in d ole (6d ). The same procedure as
above was carried out by using 12d to give the MOM ether
6d (74%): oil; IR (neat) 3279, 2116 cm-1; 1H NMR δ 2.60 (d, 1
H, J ) 2 Hz), 3.29 (s, 3 H), 3.36 (s, 3 H); 4.53 (d, 1 H, J ) 7
Hz), 5.42 (dd, 1 H, J ) 2, 11 Hz), 5.65 (s, 2 H), 5.65 (dd, 1 H,
J ) 2, 18 Hz), 5.92 (d, 1 H, J ) 2 Hz), 6.91 (dd, 1 H, J ) 11,
18 Hz), 7.05-7.83 (m, 4 H); MS m/ z 285 (M+). HRMS Calcd
for C17H19NO3: 285.1364. Found: 285.1372.
P r ep a r a tion of th e Ca r ba zoles 4 a n d 13. A typical
example of 4a and 13a is represented as follows, and other
examples of 4b-d show the compound name, yield, and
physical data.
3-E t h e n yl-N -(m e t h oxym e t h yl)in d ole -2-ca r b oxa ld e -
h yd e (7d ). A similar cross-coupling reaction between 8b and
11b was carried out as above to give the 3-(ethoxyethenyl)-
1
indole 7d (89%): oil; IR (KBr) 1611 cm-1; H NMR δ 3.27 (s,
3 H), 5.61 (d, 1 H, J ) 10 Hz), 5.89 (d, 1 H, J ) 10 Hz), 5.88
(s, 2 H), 6.94-7.91 (m, 5 H), 10.08 (s, 1 H); MS m/ z 215 (M+).
HRMS Calcd for C13H13NO2: 215.0946. Found: 215.0953.
Rea ction of th e 2-F or m ylin d ole 7 w ith Eth yn ylm a g-
n esiu m Br om id e. A typical example of 12a is represented
as follows, and other examples of 12b-d show the compound
name, yield, and physical data.
N -(B e n ze n e s u lfo n y l)-3-(2-e t h o x y e t h e n y l)-2-(1-h y -
d r oxyp r op -2-yn -1-yl)in d ole (12a ). An ice-cooled solution of
ethynylmagnesium bromide (1.0 M in THF, 9.1 mL, 9.14 mmol)
was added to a solution of (ethoxyethenyl)indole 7a (500 mg,
1.41 mmol) in THF (15 mL). After stirring at rt for 2 h, the
mixture was treated with aqueous NH4OH solution (saturated)
and extracted with EtOAc. The EtOAc layer was washed with
brine, dried over Na2SO4, and concentrated. The residue was
purified by column chromatography (silica gel, 30 g) using
EtOAc-hexane (3:17, v/v) as an eluent to give the propargyl
alcohol 12a (501 mg, 82%) as an oil: IR (neat) 3288, 2116,
1369, 1024 cm-1; 1H NMR δ 1.33 (t, 3 H, J ) 7 Hz), 2.60 (d, 1
H, J ) 3 Hz), 3.97 (q, 2 H, J ) 7 Hz), 4.39 (br d, 1 H, J ) 10
Hz, exchangeable with D2O), 5.81 (d, 1 H, J ) 8 Hz), 5.99 (br
dd, 1 H, J ) 3, 10 Hz), 6.90 (d, 1 H, J ) 8 Hz), 7.01-8.03 (m,
9 H); MS m/ z 381 (M+). HRMS Calcd for C21H19NO4S:
381.1034. Found: 381.1045.
N-(Ben zen esu lfon yl)-3-eth en yl-2-(1-h yd r oxyp r op -2-yn -
1-yl)in d ole (12b). The same procedure as above was carried
out by using 7b (99%): oil, IR (neat) 3496, 3282, 2118, 1367

2540 J . Org. Chem., Vol. 62, No. 8, 1997
Choshi et al.
N-(Ben zen esu lfon yl)-3-eth oxy-1-[(m eth oxym eth yl)oxy]-
2-m eth ylca r ba zole (4a ) a n d 3-Eth oxy-1-[(m eth oxym eth -
yl)oxy]-2-m eth ylca r ba zole (13a ). A solution of the MOM
ether 6a (310 mg, 0.73 mmol) in THF (1 mL) was added to a
solution of t-BuOK (245 mg, 2.2 mmol) in t-BuOH (4 mL). The
stirred solution was heated at 90 °C for 3 h. After being cooled
to rt, the solution was treated with aqueous NH4Cl solution
(saturated). The mixture was extracted with EtOAc. The
EtOAc layer was washed with brine, dried over Na2SO4, and
concentrated. The residue was purified by column chroma-
tography (silica gel, 20 g) using EtOAc-hexane (1:19, v/v) as
an eluent to give the N-(benzenesulfonyl)carbazole 4a (126 mg,
41%) and the carbazole 13a (89 mg, 43%), respectively.
4a : mp 131.5-133 °C (from Et2O-hexane); IR (KBr) 1363
cm-1; 1H NMR δ 1.40 (t, 3 H, J ) 7 Hz), 2.30 (s, 3 H), 3.49 (s,
3 H), 3.97 (q, 2 H, J ) 7 Hz), 5.38 (s, 2 H), 6.75 (s, 1 H), 6.83-
7.59 (m, 8 H), 8.00-8.26 (m, 1 H); MS m/ z 425 (M+). Anal.
Calcd for C23H23NO5S: C, 64.92; H, 5.45; N, 3.29. Found: C,
65.04, H, 5.46; N, 3.15.
tography (silica gel, 20 g) using EtOAc-hexane (1:9, v/v) as
an eluent to give the MOM ether 15 (1.2 g, 89%) as an oil: IR
(neat) 3261, 2110 cm-1
;
1H NMR δ 2.65 (d, 1 H, J ) 2 Hz),
3.30 (s, 3 H), 3.41 (s, 3 H), 4.56 (d, 1 H, J ) 6 Hz), 4.87 (d, 1
H, J ) 6 Hz), 5.74 (s, 2 H), 5.95 (d, 1 H, J ) 2 Hz), 7.02-7.63
(m, 4 H); MS m/ z 385 (M+). HRMS Calcd for C15H16NO3I:
385.0174. Found: 385.0193.
3-Iodo-N-(m eth oxym eth yl)-2-[1-[(m eth oxym eth yl)oxy]-
a llen -1-yl]in d ole (16). A stirred solution of the MOM ether
15 (40 mg, 0.1 mmol) in THF (0.5 mL) was added to a solution
of t-BuOK (35 mg, 0.31 mmol) in t-BuOH (3 mL). The solution
was heated at 90 °C for 3 h. After being cooled to rt, the
solution was treated with aqueous NH4Cl solution (saturated).
The mixture was extracted with EtOAc. The EtOAc layer was
washed with brine, dried over Na2SO4, and concentrated. The
residue was purified by column chromatography using EtOAc-
hexane (1:4, v/v) as an eluent to give the allenylindole 16 (33
mg, 83%) as an oil: IR (neat) 1961 cm-1; 1H NMR δ 3.25 (s, 3
H), 3.50 (s, 3 H), 4.99 (s, 2 H), 5.57 (s, 2 H), 5.62 (s, 2 H), 7.02-
13a : IR (neat) 3331 cm-1
;
1H NMR δ 1.49 (t, 3 H, J ) 7
7.64 (m, 4 H); MS m/ z 385 (M+). HRMS Calcd for C15H16
-
NO3I: 385.0174. Found: 385.0168.
P r ep a r a tion of th e 1-Hyd r oxyca r ba zoles 17, 18, a n d
23 fr om th e O-MOM Eth er s 4b a n d 13a ,b. A typical
example of 23 is represented as follows, and other examples
of 17 and 18 show the compound name, yield, and physical
data.
Hz), 2.34 (s, 3 H), 3.67 (s, 3 H), 4.10 (q, 2 H, J ) 7 Hz), 5.13 (s,
2 H), 6.87-7.40 (m, 4 H), 7.78-7.99 (m, 1 H), 8.97 (br s, 1 H);
MS m/ z 285 (M+). HRMS Calcd for C17H19NO3: 285.1364.
Found: 285.1378.
N-(Ben zen esu lfon yl)-1-[(m eth oxym eth yl)oxy]-2-m eth -
ylca r ba zole (4b) a n d 1-[(m eth oxym eth yl)oxy]-2-m eth yl-
ca r ba zole (13b). The same procedure as above was carried
out by using 6b to give the N-(benzenesulfonyl)carbazole 4b
(20%) and the carbazole 13b (57%), respectively.
4b: mp 137-139.5 °C (from EtOAc-hexane); IR (KBr) 1373
cm-1; 1H NMR δ 2.44 (s, 3 H), 3.50 (s, 3 H), 5.36 (s, 2 H), 6.78-
7.72 (m, 10 H), 8.05-8.28 (m, 1 H); MS m/ z 381 (M+). Anal.
Calcd for C21H19NO4S: C, 66.12; H, 5.02; N, 3.67. Found: C,
66.29; H, 4.98; N, 3.69.
3-Eth oxy-1-h yd r oxy-2-m eth ylca r ba zole (23). TMSCl
(160 µL, 1.26 mmol) was added to a stirred suspension of the
carbazole 13a (239 mg, 0.84 mmol) and NaI (189 mg, 1.26
mmol) in MeCN (8 mL) at -20 °C. After the further addition
of TMSCl (105 µL, 0.84 mmol) and NaI (124 mg, 0.84 mmol)
at -20 °C, the mixture was stirred for 5 min and then the
mixture was treated with MeOH. After removal of the solvent,
water and EtOAc were added to the residue for extraction.
The EtOAc layer was washed with 10% aqueous Na2CO3
solution and brine and then dried over Na2SO4. The organic
layer was concentrated, and the residue was purified by
column chromatography (silica gel, 20 g) using EtOAc-hexane
(3:17, v/v) as an eluent to give the 1-hydroxycarbazole 23 (127
mg, 63%): mp 153-155 °C (from CH2Cl2-light petroleum);
13b: oil; 1H NMR δ 2.40 (s, 3 H), 3.67 (s, 3 H), 5.15 (s, 2 H),
6.91 (d, 1 H, J ) 8 Hz), 6.95-7.53 (m, 3 H), 7.62 (d, 1 H, J )
8 Hz), 7.84-8.07 (m, 1 H), 9.20 (br s, 1 H); MS m/ z 241 (M+).
HRMS Calcd for C15H15NO2: 241.1102. Found: 241.1099.
3-Eth oxy-N-(m eth oxym eth yl)-1-[(m eth oxym eth yl)oxy]-
2-m eth ylca r ba zole (4c). The same procedure as above was
carried out by using 6c to give the N,O-bis(methoxymethyl)-
carbazole 4c (92%): oil; 1H NMR δ 1.46 (t, 3 H, J ) 7 Hz),
2.35 (s, 3 H), 3.24 (s, 3 H), 3.53 (s, 3 H), 4.08 (q, 2 H, J ) 7
Hz), 5.08 (s, 2 H), 5.89 (s, 2 H), 6.99-7.94 (m, 5 H); MS m/ z
329 (M+). HRMS Calcd for C19H23NO4: 329.1626. Found:
329.1638.
1
IR (KBr) 3154, 3346 cm-1; H NMR δ 1.44 (t, 3 H, J ) 7 Hz),
2.25 (br s, 3 H), 4.08 (q, 2 H, J ) 7 Hz), 4.88 (br s, 1 H,
exchangeable with D2O), 6.91-7.40 (m, 3 H), 7.25 (s, 1 H),
7.73-8.08 (m, 1 H); MS m/ z 241 (M+), 212 (M+ - 28). Anal.
Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.80. Found: C,
74.60; H, 6.41; N, 6.00.
N-(Ben zen esu lfon yl)-1-h ydr oxy-2-m eth ylcar bazole (17).
The same procedure as above was carried out by using 4b to
give the 1-hydroxycarbazole 17 (94%): mp 116-118 °C (from
CH2Cl2-light petroleum); IR (KBr) 3155, 1370 cm-1; 1H NMR
δ 2.43 (s, 3 H), 6.73-7.65 (m 10 H), 8.06-8.29 (m, 1 H), 9.20
(br s, 1 H, exchangeable with D2O); MS m/ z 337 (M+). Anal.
Calcd for C19H15NO3S: C, 67.64; H, 4.48; N, 4.15. Found: C,
67.69; H, 4.35; N, 4.01.
N-(Met h oxym et h yl)-1-[(m et h oxym et h yl)oxy]-2-m et h -
ylca r ba zole (4d ). The same procedure as above was carried
out by using 6d to give the N,O-bis(methoxymethyl)carbazole
4d (96%): oil; 1H NMR δ 2.48 (s, 3 H), 3.32 (s, 3 H), 3.62 (s, 3
H), 5.15 (s, 2 H), 5.97 (m, 6 H); MS m/ z 285 (M+). HRMS
Calcd for C17H19NO3: 285.1364. Found: 285.1360.
2-(1-Hyd r oxyp r op -2-yn -1-yl)-3-iod o-N-(m eth oxym eth -
yl)in d ole (14). A solution of ethynylmagnesium bromide (0.5
M in THF, 7.0 mL, 3.5 mmol) was added to an ice-cooled
solution of N-MOM-indole 8b in THF (15 mL) under stirring.
After stirring at 0 °C for 1 h, the solution was extracted with
EtOAc. The EtOAc layer was washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by
column chromatography (silica gel, 30 g) using EtOAc-hexane
(3:7, v/v) as an eluent to give the propargyl alcohol 14 (1.07 g,
99%): mp 101-102 °C (from Et2O-hexane); IR (KBr) 3291,
1-Hyd r oxy-2-m eth ylca r ba zole (18). The same procedure
as above was carried out by using 13b to give the 1-hydroxy-
carbazole 18 (85%): mp 145-146.5 °C (from CH2Cl2-hexane);
1
IR (KBr) 3158 cm-1; H NMR δ 2.34 (s, 3 H), 4.71 (br s, 1 H,
exchangeable with D2O), 6.80-7.68 (m, 5 H), 7.83-8.25 (m, 1
H); MS m/ z 197 (M+). Anal. Calcd for C13H11NO: C, 79.17;
H, 5.62; N, 7.10. Found: C, 79.24; H, 5.73; N, 6.99.
P r ep a r a tion of th e O-Tr ifla tes 19, 20, a n d 24. A typical
example of 24 is represented as follows, and other examples
of 19 and 20 show the compound name, yield, and physical
data.
1
2110 cm-1; H NMR δ 2.63 (d, 1 H, J ) 2 Hz), 3.28 (s, 3 H),
4.00 (br d, 1 H, J ) 8 Hz, exchangeable with D2O), 5.52 (d, 1
H, J ) 8 Hz), 5.82 (dd, 1 H, J ) 2, 8 Hz), 6.15 (d, 1 H, J ) 8
Hz), 7.10-7.65 (m, 4 H); MS m/ z 341 (M+). Anal. Calcd for
C13H12NO2I: C, 45.77; H, 3.55, N, 4.11. Found: C, 45.78; H,
3.58; N, 4.08.
3-Eth oxy-2-m eth yl-1-[(tr iflu or om eth a n esu lfon yl)oxy]-
ca r ba zole (24). Tf2O (55 µL, 0.33 mmol) was added to a
stirred solution of the 1-hydroxycarbazole 23 (66 mg, 0.27
mmol) and pyridine (66 µL, 0.81 mmol) in CH2Cl2 under cooling
with ice. After stirring at rt for 2 h, the solution was treated
with water. The mixture was extracted with CH2Cl2. The
CH2Cl2 layer was washed with water and brine and then dried
over Na2SO4. The solvent was removed, and the residue was
purified by column chromatography (silica gel, 20 g) using
EtOAc-hexane (1:19, v/v) as an eluent to give the triflate 24
(85%): mp 131-132 °C (from CH2Cl2-hexane); IR (KBr) 1400,
3-Iodo-N-(m eth oxym eth yl)-2-[1-[(m eth oxym eth yl)oxy]-
p r op -2-yn -1-yl]in d ole (15). A stirred solution of the prop-
argyl alcohol 14 (1.2 g, 3.5 mmol), MOMCl (1.87 mL, 24.6
mmol), and i-Pr2NEt (4.9 mL, 28.0 mmol) in CH2Cl2 (30 mL)
was heated at 50 °C for 12 h. The solution was treated with
water, and the mixture was extracted with CH2Cl2. The CH2-
Cl2 layer was washed with brine, dried over Na2SO4, and
concentrated. The residue was purified by column chroma-

Carazostatin, Hyellazole, and Carbazoquinocins
J . Org. Chem., Vol. 62, No. 8, 1997 2541
1
1073 cm-1; H NMR δ 1.44 (t, 3 H, J ) 7 Hz), 2.34 (s, 3 H),
4.14 (q, 2 H, J ) 6.7 Hz), 7.17 (t, 1 H, J ) 7.6 Hz), 7.35 (t, 1
H, J ) 7.6 Hz), 7.38 (s, 1 H), 7.42 (d, 1 H, J ) 7.6 Hz), 7.76 (br
s, 1 H) 7.97 (d, 1 H, J ) 7.6 Hz); MS m/ z 323 (M+). Anal.
Calcd for C22H29NO: C, 81.69; H, 9.04; N, 4.33. Found: C,
81.71; H, 8.94; N, 4.49.
4.06 (q, 2 H, J ) 7 Hz), 6.99-7.44 (m, 3 H), 7.23 (s, 1 H), 7.70-
8.12 (m, 1 H); MS m/ z 373 (M+). Anal. Calcd for C16H14
-
NO4F3S: C, 51.47; H, 3.78; N, 3.75. Found: C, 51.63; H, 3.59;
N, 3.82.
N-(Ben zen esu lfon yl)-2-m et h yl-1-[(t r iflu or om et h a n e-
su lfon yl)oxy]ca r ba zole (19). The same procedure as above
was carried out by using 17 to give the triflate 19 (96%): mp
3-Eth oxy-2-m eth yl-1-p h en ylca r ba zole (25b). A stirred
suspension of the triflate 24 (49 mg, 0.13 mmol), phenylboronic
acid (19 mg, 0.16 mmol), 2 M Na2CO3 (0.13 mL, 0.26 mmol),
and Pd(PPh3)4 (8 mg, 0.007 mmol) in DME (1 mL) was heated
at 100 °C for 1 h. After being cooled to rt, the mixture was
treated with water, and then the mixture was extracted with
EtOAc. The EtOAc layer was washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by
column chromatography (silica gel, 10 g) using EtOAc-hexane
(1:9, v/v) as an eluent to give the 1-phenylcarbazole 25b (38
mg, 96%) as an oil: 1H NMR δ 1.49 (t, 3 H, J ) 7 Hz), 2.23 (s,
3 H), 4.20 (q, 2 H, J ) 7 Hz), 7.00-7.58 (m, 4 H), 7.43 (s, 5 H),
7.77-8.01 (m, 1 H); MS m/ z 301 (M+). HRMS Calcd for
C21H19NO: 301.1466. Found: 301.1482.
1
153-155 °C (from Et2O); IR (KBr) 1419, 1080 cm-1; H NMR
δ 2.26 (s, 3 H), 6.91-7.74 (m, 10 H), 7.99-8.25 (m, 1 H); MS
m/ z 469 (M+). Anal. Calcd for C20H14NO5F3S2: C, 51.17; H,
3.01; N, 2.98. Found: C, 51.06; H, 2.89; N, 3.11.
1-[(Tr iflu or om e t h a n e su lfon yl)oxy]-2-m e t h ylca r b a -
zole (20). The same procedure as above was carried out by
using 18 to give the triflate 20 (98%): mp 86-87 °C (from
1
light petroleum ether); IR (KBr) 1406, 1070 cm-1; H NMR δ
2.49 (s, 3 H), 6.95 (d, 1 H, J ) 8 Hz), 7.00-7.46 (m, 3 H), 7.78-
8.02 (m, 1 H), 7.80 (d, 1 H, J ) 8 Hz), 8.19 (br s, 1 H); MS m/ z
329 (M+). Anal. Calcd for C14H10NO3F3S: C, 51.06; H, 3.06;
N, 4.25. Found: C, 51.15; H, 2.87; N, 4.26.
1-Hep tyl-3-h yd r oxy-2-m eth ylca r ba zole (Ca r a zosta tin ,
1). A solution of BBr3 (29 µL, 0.31 mmol) in CH2Cl2 (2 mL)
was added at -78 °C to a stirred solution of 3-ethoxycarbazole
25a (50 mg, 0.15 mmol) in CH2Cl2 (2 mL). After being warmed
to rt gradually, the solution was stirred for 4 h and then
treated with water. The mixture was extracted with EtOAc.
The EtOAc layer was washed with brine, dried over Na2SO4,
and concentrated. The residue was purified by column chro-
matography (silica gel, 20 g) using EtOAc-hexane (1:9, v/v)
as an eluent to give the carazostatin (1) (41 mg, 90%): mp
159-160 °C (from CH2Cl2-light petroleum) (lit.4,5 mp 162-
1-Hep tyl-2-m eth ylca r ba zole (22). A solution of 9-heptyl-
9-BBN (21) [prepared from 1-heptene (38 µL, 0.27 mmol) in
THF (1 mL) with 9-BBN (0.5 M in THF, 0.54 mL, 0.27 mmol)
at rt for 4 h] was added by cannula to a stirred suspension of
the triflate 20 (60 mg, 0.18 mmol), 3 M NaOH (0.18 mL, 0.54
mmol), and PdCl2(dppf) (9 mg, 0.014 mmol) in THF (1.5 mL).
The mixture was heated at 80 °C for 3 h. After being cooled
to rt, the mixture was treated with water and EtOAc. The
EtOAc layer was separated, washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by
column chromatography (silica gel, 10 g) using EtOAc-hexane
(2:98, v/v) as an eluent to give the 1-heptylcarbazole 22 (27
mg, 53%): mp 50-52 °C (from hexane); 1H NMR (500 MHz) δ
0.90 (t, 3 H, J ) 7.2 Hz), 1.15-1.70 (m, 10 H), 2.48 (s, 3 H),
2.88 (t, 2 H, J ) 7.9 Hz), 7.04 (d, 1 H, J ) 8 Hz), 7.20 (t, 1 H,
J ) 7.3 Hz), 7.38 (t, 1 H, J ) 7.3 Hz), 7.44 (d, 1 H, J ) 7.3
Hz), 7.79 (d, 1 H, J ) 8 Hz), 8.00 (d, 1 H, J ) 7.3 Hz); MS m/ z
279 (M+). Anal. Calcd for C20H25N: C, 85.97; H, 9.02; N, 5.01.
Found: C, 86.03; H, 9.06; N, 4.87.
1
163 °C); IR (KBr) 3350 cm-1; H NMR (400 MHz) δ 0.90 (t, 3
H, J ) 6.8 Hz), 1.20-1.50 (m, 8 H), 1.60-1.69 (m, 2 H), 2.38
(s, 3 H), 2.89 (t, 2 H, J ) 7 Hz), 7.17 (t, 1 H, J ) 7 Hz), 7.31
(s, 1 H), 7.33-7.46 (m, 2 H), 7.74 (br s, 1 H), 7.94 (d, 1 H, J )
7 Hz); MS m/ z 295 (M+). Anal. Calcd for C20H25NO: C, 81.31;
H, 8.53; N, 4.74. Found: C, 81.33; H, 8.72; N, 4.81.
3-Hydr oxy-2-m eth yl-1-ph en ylcar bazole (26).3i The same
procedure as above was carried out by using 25b to give the
hydroxycarbazole 26 (90%). The solvent system for column
chromatography used EtOAc-hexane (15:85, v/v): mp 171-
3-E t h oxy-1-[(m e t h oxym e t h yl)oxy]-2-m e t h ylca r b a -
zole (13a ) fr om 4a . A mixture of the N-(benzenesulfonyl)-
carbazole 4a (833 mg, 1.96 mmol) and aqueous 3 M NaOH
solution (30 mL, 90 mmol) in MeOH (50 mL) and THF (15
mL) was refluxed for 18 h. After being cooled to rt, the mixture
was acidified with concd HCl. The mixture was extracted with
EtOAc. The EtOAc layer was washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by
column chromatography (silica gel, 20 g) using EtOAc-hexane
(5:95, v/v) as an eluent to give the carbazole 13a (550 mg, 98%).
3-E t h oxy-1-[(m e t h oxym e t h yl)oxy]-2-m e t h ylca r b a -
zole (13a ) fr om 4c. A solution of N-[(methoxymethyl)oxy]-
carbazole 4c (85 mg, 0.258 mmol) and 1 M HCl (1 mL) in
i-PrOH (1 mL) and THF (2 mL) was refluxed for 15 h. After
being cooled to rt, the solution was neutralized with aqueous
Na2CO3 solution (saturated). The mixture was extracted with
EtOAc. The EtOAc layer was washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by
column chromatography (silica gel, 5 g) using EtOAc-hexane
(1:19, v/v) as an eluent to give the carbazole 13a (45 mg, 61%).
3-Eth oxy-1-h ep tyl-2-m eth ylca r ba zole (25a ). A solution
of 9-heptyl-9-BBN [prepared from 9-BBN (0.5 M in THF, 0.58
mL, 0.29 mmol) and 1-heptene (40 µL, 0.29 mmol) in THF (1
mL) at 0 °C for 4 h] was added to a mixture of the triflate 24
(71 mg, 0.19 mmol), 3 M NaOH (0.19 mL, 0.57 mmol), and
PdCl2(dppf) (6 mg, 0.01 mmol) in THF (1.5 mL) by cannula.
The stirred mixture was heated at 80 °C for 1.5 h. After being
cooled to rt, the mixture was treated with aqueous 30% H2O2
solution (3 mL) and aqueous 3 M AcONa solution (3 mL). The
mixture was further stirred for 30 min and then extracted with
EtOAc. The EtOAc layer was washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by
column chromatography (silica gel, 10 g) using EtOAc-hexane
(1:19 v/v) as an eluent to give the 1-heptylcarbazole 25a (52
1
173 °C (from CHCl3-hexane); IR (KBr) 3310 cm-1; H NMR
(400 MHz) δ 2.23 (s, 3 H), 7.16 (t, 1 H, J ) 7 Hz), 7.26-7.57
(m, 7 H), 7.48 (s, 1 H), 7.58 (br s, 1 H), 7.97 (d, 1 H, J ) 7.8
Hz); MS m/ z 273 (M+). Anal. Calcd for C19H15NO: C, 83.49;
H, 5.53; N, 5.12. Found: C, 83.52; H, 5.69; N, 4.98.
Hyella zole (2a ). A stirred suspension of 3-hydroxycarba-
zole 26 (13 mg, 0.048 mmol), CH3I(1.26 mL, 20.3 mmol), and
K2CO3 (134 mg, 0.96 mmol) in Me2CO (10 mL) was heated at
60 °C for 12 h. After being cooled to rt, the solvent was
removed. The residue was extracted with EtOAc. The EtOAc
layer was washed with brine, dried over Na2SO4, and concen-
trated. The residue was purified by column chromatography
(silica gel, 10 g) using EtOAc-hexane (1:19, v/v) as an eluent
to give the hyellazole (2a ) (13 mg, 95%): mp 129-130 °C (from
hexane) (lit.2,3 mp 133-134 °C); IR (KBr) 3310 cm-1; 1H NMR
(400 MHz) δ 2.21 (s, 3 H), 4.00 (s, 3 H), 7.18 (t, 1 H, J ) 6.9
Hz), 7.24-7.56 (m, 7 H), 7.51 (s, 1 H), 7.60 (br s, 1 H), 8.02 (d,
1 H, J ) 7.8 Hz); MS m/ z 287 (M+). Anal. Calcd for C20H17
-
NO: C, 83.60; H, 5.96; N, 4.87. Found: C, 83.45; H, 6.01; N,
4.74.
Ca r ba zoqu in ocin C (3c). A solution of carazostatin (1)
(22 mg, 0.074 mmol) in THF (1 mL) was added to a stirred
suspension of 70% (PhSeO)2O (38 mg, 0.074 mmol) in THF (3
mL). The mixture was stirred at 50 °C for 30 min. After being
cooled to rt, the reaction mixture was diluted with MeOH-
CHCl3 (1:9) (50 mL). The mixture was washed with aqueous
10% Na2CO3 solution, water, and brine. The CHCl3 layer was
dried over Na2SO4 and concentrated. The residue was purified
by column chromatography (silica gel, 10 g) using EtOAc as
an eluent to give the carbazoquinocin C (3c) (22 mg, 95%):
mp 227-229 °C (from EtOAc) (lit.6 mp 210-212 °C); IR (KBr)
1649, 1632, 1474, 1256, 760 cm-1; 1H NMR (500 MHz, DMSO-
d6) δ 0.86 (t, 3 H, J ) 7.1 Hz), 1.22-1.38 (m, 6 H), 1.42-1.49
(m, 2 H), 1.52-1.60 (m, 2 H), 1.91 (s, 3 H), 2.67 (t, 2 H, J )
7.5 Hz), 7.22-7.26 (m, 2 H), 7.50-7.53 (m, 1 H), 7.85-7.86
(m, 1 H); 13C NMR (125 MHz, DMSO-d6) δ 183.5, 172.6, 145.8,
1
mg, 85%): mp 80.5-82.5 °C (from pentane); H NMR δ 0.87
(t, 3 H, J ) 7.1 Hz), 1.24-1.39 (m, 7 H), 1.42-1.54 (m, 2 H),
1.49 (t, 3 H, J ) 6.7 Hz), 2.36 (s, 3 H), 2.88 (t, 2 H, J ) 7.9 Hz,

2542 J . Org. Chem., Vol. 62, No. 8, 1997
Choshi et al.
142.2, 137.2, 133.0, 125.7, 124.0, 123.8, 120.2, 113.4, 111.0,
31.2, 28.9, 28.5, 28.4, 28.0, 22.0, 13.8, 11.4; MS m/ z 311 (M+
+ 2), 309 (M+). Anal. Calcd for C20H23NO2: C, 77.64; H, 7.49;
N, 4.53. Found: C, 77.55; H, 7.60; N, 4.51.
Cr oss-Cou p lin g Rea ction betw een th e Tr ifla te 24 a n d
9-Alk yl-9-BBN 27. A typical example of 28a is represented
as follows, and other examples of 28b-d show the compound
name, yield, and physical data.
Clea va ge of th e Eth yl Eth er 28 by BBr 3. A typical
example of 29a is represented as follows, and other examples
of 29b-d show the compound name, yield, and physical data.
3-Hydr oxy-2-m eth yl-1-(5-m eth oxyh exyl)car bazole (29a).
A solution of BBr3 (27 µL, 0.29 mmol) in CH2Cl2 (12 mL) was
added at -78 °C to a stirred solution of 3-ethoxycarbazole 28a
(47 mg, 0.15 mmol) in CH2Cl (3 mL). After being warmed to
rt gradually, the mixture was extracted with EtOAc. The
EtOAc was washed with brine, dried over Na2SO4, and
concentrated. The residue was purified by column chroma-
tography (silica gel, 10 g) using EtOAc-hexane (3:17, v/v) as
an eluent to give the 3-hydroxycarbazole 29a (39 mg, 91%):
mp 157-159 °C (from CH2Cl2-light petroleum); IR (KBr) 3473,
3-Eth oxy-2-m eth yl-1-(5-m eth ylh exyl)ca r ba zole (28a ). A
solution of 9-(5-methylhexyl)-9-BBN (27a ) [prepared from
9-BBN (0.5 M n THF, 0.96 mL, 0.48 mmol) and 5-methyl-1-
hexene (68 µL, 0.48 mmol) in THF (1 mL) at 0 °C for 4 h] was
added to a mixture of the triflate 24 (91 mg, 0.24 mmol), 3 M
NaOH (0.24 mL, 0.72 mmol), and PdCl2(dppf) (8 mg, 0.012
mmol) in THF (1.5 mL) by cannula. The stirred mixture was
heated at 80 °C for 1.5 h. After being cooled to rt, the mixture
was treated with aqueous 30% H2O2 solution (3 mL) and
aqueous 3 M AcONa solution (3 mL). The mixture was further
stirred for 30 min and then extracted with EtOAc. The EtOAc
was washed with brine, dried over Na2SO4, and concentrated.
The residue was purified by column chromatography (silica
gel, 20 g) using EtOAc-hexane (1:19 v/v) as an eluent to give
the 1-(5-methylhexyl)carbazole 28a (60 mg, 76%): mp 79-81
°C (from pentane); 1H NMR (500 MHz) δ 0.88 (d, 6 H, J ) 6.7
Hz), 1.22-1.28 (m, 2 H), 1.43-1.51 (m, 2 H), 1.49 (t, 3 H, J )
7 Hz), 1.52-1.67 (m, 3 H), 2.41 (s, 3 H), 2.88 (t, 2 H, J ) 7.9
Hz), 4.13 (q, 2 H, J ) 7 Hz), 7.17 (t, 1 H, J ) 7.9 Hz), 7.35 (t,
1 H, J ) 7.9 Hz), 7.38 (s, 1 H), 7.42 (d, 1 H, J ) 7.9 Hz), 7.76
(br s, 1 H), 7.97 (d, 1 H, J ) 7.9 Hz); MS m/ z 323 (M+). Anal.
Calcd for C22H29NO: C, 81.69; H, 9.04; N, 4.33. Found: C,
81.50; H, 9.11; N, 4.36.
3-Eth oxy-2-m eth yl-1-(5-m eth ylh ep tyl)ca r ba zole (28b).
The same procedure as above was carried out by using 9-(5-
methylheptyl)-9-BBN (27b) (prepared from 9-BBM and 5-meth-
yl-1-heptane20) (78%): mp 72-74 °C (from pentane); 1H NMR
(500 MHz) δ 0.86 (d, 3 H, J ) 6.4 Hz), 0.87 (t, 3 H, J ) 8.5
Hz), 1.13-1.19 (m, 2 H), 1.31-1.54 (m, 5 H), 1.49 (t, 3 H, J )
7 Hz), 1.59-1.66 (m, 2 H), 2.36 (s, 3 H), 2.89 (t, 2 H, J ) 8
Hz), 4.14 (q, 2 H, J ) 7 Hz), 7.17 (t, 1 H, J ) 7.5 Hz), 7.35 (t,
1 H, J ) 7.5 Hz), 7.38 (s, 1 H), 7.42 (d, 1 H, J ) 7.5 Hz), 7.76
(br s, 1 H), 7.87 (d, 1 H, J ) 7.5 Hz); MS m/ z 337 (M+). Anal.
Calcd for C23H31NO: C, 81.85; H, 9.26; N, 4.15. Found: C,
81.89; H, 9.35; N, 3.99.
1
3379 cm-1; H NMR (500 MHz) δ 0.89 (d, 6 H, J ) 6.7 Hz),
1.23-1.28 (m, 2 H), 1.44-1.50 (m, 2 H), 1.52-1.67 (m, 3 H),
2.37 (s, 3 H), 2.88 (t, 2 H, J ) 7.9 Hz), 7.16 (t, 1 H, J ) 7 Hz),
7.33 (s, 1 H), 7.36 (t, 1 H, J ) 7 Hz), 7.41 (d, 1 H, J ) 7 Hz),
7.74 (br s, 1 H), 7.93 (d, 1 H, J ) 7 Hz); MS m/ z 295 (M+).
Anal. Calcd for C20H25NO: C, 81.31; H, 8.53; N, 4.74.
Found: C, 81.25; H, 8.54; N, 4.60.
3-Hydr oxy-2-m eth yl-1-(5-m eth ylh eptyl)car bazole (29b).
The same procedure as above was carried out by using 28b
(97%): mp 162-164 °C (from CH2Cl2-light petroleum); IR
1
(KBr) 3475, 3369 cm-1; H NMR (500 MHz) δ 0.86 (d, 3 H, J
) 6.4 Hz), 0.87 (t, 3 H, J ) 7.3 Hz), 1.12-1.21 (m, 2 H), 1.28-
1.54 (m, 5 H), 1.59-1.67 (m, 2 H), 2.37 (s, 3 H), 2.89 (t, 2 H,
J ) 7.9 Hz), 7.16 (t, 1 H, J ) 7 Hz), 7.33 (s, 1 H), 7.35 (t, 1 H,
J ) 7 Hz), 7.41 (d, 1 H, J ) 7 Hz), 7.74 (br s, 1 H), 7.93 (d, 1
H, J ) 7 Hz); MS m/ z 309 (M+). Anal. Calcd for C21H27NO:
C, 81.51; H, 8.79; N, 4.52. Found: C, 81.49; H, 8.79; N, 4.56.
3-Hydr oxy-2-m eth yl-1-(6-m eth ylh eptyl)car bazole (29c).
The same procedure as above was carried out by using 28c
(64%): mp 163-165 °C (from CHCl3-hexane); IR (KBr) 3474,
1
3367 cm-1; H NMR (500 MHz) δ 0.87 (d, 6 H, J ) 6.4 Hz),
1.15-1.20 (m, 2 H), 1.35-1.37 (m, 2 H), 1.39-1.47 (m, 2 H),
1.51-1.57 (m, 1 H), 1.62-1.69 (m, 2 H), 2.37 (s, 3 H), 2.88 (t,
2 H, J ) 8.1 Hz), 4.54 (br s, 1 H), 7.16 (t, 1 H, J ) 8 Hz), 7.33
(s, 1 H), 7.35 (t, 1 H, J ) 8 Hz), 7.41 (d, 1 H, J ) 8 Hz), 7.74
(br s, 1 H), 7.93 (d, 1 H, J ) 8 Hz); MS m/ z 309 (M+). Anal.
Calcd for C21H27NO: C, 81.51; H, 8.79; N, 4.52. Found: C,
81.62; H, 8.60; N, 4.67.
3-Hyd r oxy-2-m eth yl-1-(7-m eth yloctyl)ca r ba zole (29d ).
The same procedure as above was carried out by using 28d
(74%): mp 160-162 °C (CHCl3-hexane); IR (KBr) 3477, 3366
3-Eth oxy-2-m eth yl-1-(6-m eth ylh ep tyl)ca r ba zole (28c).
The same procedure as above was carried out by using 9-(6-
methylheptyl)-9-BBN (27c) (prepared from 9-BBM and 6-meth-
yl-1-heptene21) (72%): mp 90.5-92.5 °C (from pentane); 1H
NMR (500 MHz) δ 0.87 (d, 6 H, J ) 6.4 Hz), 1.16-1.20 (m, 2
H), 1.32-1.38 (m, 2 H), 1.41-1.46 (m, 2 H), 1.49 (t, 3 H, J )
7 Hz), 1.63-1.69 (m, 2 H), 2.36 (s, 3 H), 2.89 (t, 2 H, J ) 7.9
Hz), 4.14 (q, 2 H, J ) 7 Hz), 7.17 (t, 1 H, J ) 8.3 Hz), 7.35 (t,
1 H, J ) 8.3 Hz), 7.38 (s, 1 H), 7.45 (d, 1 H, J ) 8.3 Hz), 7.76
(br s, 1 H), 7.97 (d, 1 H, J ) 8.3 Hz); MS m/ z 337 (M+). Anal.
Calcd for C23H31NO: C, 81.85; H, 9.26; N, 4.15. Found: C,
82.01; H, 9.13; N, 4.18.
1
cm-1; H NMR (500 MHz) δ 0.86 (d, 6 H, J ) 6.4 Hz), 1.15-
1.18 (m, 2 H), 1.25-1.34 (m, 4 H), 1.43-1.53 (m, 3 H), 1.60-
1.68 (m, 2 H), 2.37 (s, 3 H), 2.87 (t, 2 H, J ) 8.1 Hz), 7.16 (t,
1 H, J ) 8 Hz), 7.31 (s, 1 H), 7.36 (t, 1 H, J ) 8 Hz), 7.40 (d,
1 H, J ) 8 Hz), 7.78 (br s, 1 H), 7.91 (d, 1 H, J ) 8 Hz); MS
m/ z 323 (M+). Anal. Calcd for C22H29NO: C, 81.69; H, 9.04;
N, 4.33. Found: C, 81.70; H, 8.95; N, 4.14.
Oxid a tion of th e 3-Hyd r oxyca r ba zole 29 to Ca r ba zo-
qu in ocin s B a n d D-F (3b,d -f). A typical procedure of 3b
is represented as follows, and other examples of 3d -f show
the compound name, yield, and physical data.
3-Eth oxy-2-m eth yl-1-(7-m eth yloctyl)ca r ba zole (28d ).
The same procedure as above was carried out by using 9-(7-
methyloctyl)-9-BBN (27d ) (prepared from 9-BBM and 7-meth-
Ca r ba zoqu in ocin B (3b). A solution of 3-hydroxycarba-
zole 29a (34 mg, 0.12 mmol) in THF (2 mL) was added to a
stirred suspension of 70% (PhSeO)2O (59 mg, 0.12 mmol) in
THF (4 mL). The mixture was stirred at 50 °C for 30 min.
After being cooled to rt, the reaction mixture was diluted with
MeOH-CHCl3 (1:9) (50 mL). The mixture was washed with
aqueous 10% Na2CO3 solution, water, and brine. The organic
layer was dried over Na2SO4 and concentrated. The residue
was purified by column chromatography (silica gel, 20 g) using
EtOAc as an eluent to give the carbazoquinocin B (3b) (32 mg,
90%): mp 240-243 °C (from EtOAc) (lit.6 mp 213-217 °C);
IR (KBr) 1639, 1624, 1466, 1250, 754 cm-1; 1H NMR (500 MHz,
DMSO-d6) δ 0.87 (t, 6 H, J ) 9.8 Hz), 1.16-1.24 (m, 2 H), 1.43-
1.55 (m, 5 H), 1.91 (s, 3 H), 2.67 (t, 2 H, J ) 8.2 Hz), 7.23-
7.27 (m, 2 H), 7.51-7.54 (m, 1 H), 7.84-7.87 (m, 1 H); 13C NMR
(125 MHz, DMSO-d6) δ 183.5, 172.7, 145.5, 142.0, 137.0, 133.0,
125.6, 124.1, 123.9, 120.2, 113.3, 111.0, 38.2, 28.7, 28.0, 27.4,
26.8, 22.4 (2C), 11.4; MS m/ z 311 (M+ + 2), 309 (M+). Anal.
Calcd for C20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C,
77.77; H, 7.36; N, 4.73.
1
yl-1-octene22) (56%): mp 70-72 °C (from pentane); H NMR
(500 MHz) δ 0.86 (d, 6 H, J ) 7.3 Hz), 1.13-1.18 (m, 2 H),
1.25-1.37 (m, 4 H), 1.40-1.55 (m, 3 H), 1.48 (t, 3 H, J ) 7
Hz), 1.60-1.67 (m, 2 H), 2.35 (s, 3 H), 2.86 (t, 2 H, J ) 8 Hz),
4.12 (q, 2 H, J ) 7 Hz), 7.17 (t, 1 H, J ) 7.4 Hz), 7.34 (t, 1 H,
J ) 7.4 Hz), 7.37 (s, 1 H), 7.40 (d, 1 H, J ) 7.4 Hz), 7.75 (br s,
1 H), 7.97 (d, 1 H, J ) 7.4 Hz); MS m/ z 351 (M+). Anal. Calcd
for C24H33NO: C, 82.00; H, 9.46; N, 3.98. Found: C, 81.96;
H, 9.48; N, 4.00.
(19) McOmie, J . F.; West, D. F. Organic Syntheses; Wiley: New
York, 1973; Collect. Vol. V, pp 412-414.
(20) Kovalev, B. G.; Rastegaeva, V. M. J . Org. Chem. USSR (Engl.
Transl.) 1982, 18, 44-47.
(21) Walborsky, H. M.; Topolski, M.; Hamdouchi, C.; Pankowski, J .
J . Org. Chem. 1992, 57, 6188-6191.
(22) Kuepper, F. W. Ger. Offen. 2,531,872, 1972; Chem. Abstr. 1977,
87, 22334k.

Carazostatin, Hyellazole, and Carbazoquinocins
J . Org. Chem., Vol. 62, No. 8, 1997 2543
Ca r ba zoqu in ocin D (3d ). The same procedure as above
was carried out by using 29b (84%): mp 231-233 °C (from
EtOAc) (lit.6 mp 208-210 °C); IR (KBr) 1639, 1625, 1465, 1249,
754 cm-1; 1H NMR (500 MHz, DMSO-d6) δ 0.82 (t, 3 H, J ) 7
Hz), 0.83 (d, 3 H, J ) 6.4 Hz), 1.09-1.18 (m, 2 H), 1.25-1.35
(m, 4 H), 1.39-1.58 (m, 3 H), 1.91 (s, 3 H), 2.67 (t, 2 H, J )
7.5 Hz), 7.21-7.27 (m, 2 H), 7.51-7.53 (m, 1 H), 7.84-7.87
(m, 1 H); 13C NMR (125 MHz, DMSO-d6) δ 183.5, 172.6, 145.7,
142.1, 137.1, 133.0, 125.6, 124.1, 123.8, 120.2, 113.3, 111.0,
35.8, 33.7, 28.8, 28.7, 28.0, 26.5, 19.0, 11.4, 11.1; MS m/ z 325
(M+ + 2), 323 (M+). Anal. Calcd for C21H25NO2: C, 77.99; H,
7.79; N, 4.33. Found: C, 77.98; H, 7.70; N, 4.15.
(m, 5 H), 1.91 (s, 3 H), 2.67 (t, 2 H, J ) 8 Hz), 7.21-7.27 (m,
2 H), 7.49-7.54 (m, 1 H), 7.83-7.89 (m, 1 H); 13C NMR (125
MHz, DMSO-d6) δ 183.4, 172.7, 145.5, 142.0, 136.0, 133.0,
125.6, 124.1, 123.9, 120.2, 113.3, 111.0, 38.3, 29.1, 28.9, 28.4,
28.0, 27.2, 26.6, 22.4 (2C), 11.4; MS m/ z 339 (M+ + 2), 337
(M+). Anal. Calcd for C22H27NO2: C, 78.30; H, 8.06; N, 4.15.
Found: C, 78.15; H, 8.08; N, 4.20.
Ack n ow led gm en t. We would like to thank Profes-
sors Haruo Seto and Kazuo Shin-ya of the University
of Tokyo (Institute of Cellular and Molecular Bio-
sciences) for sending us authentic carbazoquinocin B.
We are also grateful to Professor Kunio Ogasawara,
Tohoku University (Pharmaceutical Institute), for pro-
viding us with samples of synthetic carazostatin and
carbazoquinocin D together with 1H and 13C NMR
spectra. This work was supported in part by Grants-
in-Aid for Scientific Research (07772122) from the
Ministry of Education, Science and Culture of J apan.
Ca r ba zoqu in ocin E (3e). The same procedure as above
was carried out by using 29c (70%): mp 226-228 °C (from
EtOAc) (lit.6 mp 209-210 °C); IR (KBr) 1639, 1624, 1468, 1259,
1
754 cm-1; H NMR (500 MHz, DMSO-d6) δ 0.85 (d, 6 H, J )
6.4 Hz), 1.14-1.19 (m, 2 H), 1.29-1.35 (m, 2 H), 1.40-1.61
(m, 5 H), 1.91 (s, 3 H), 2.67 (t, 2 H, J ) 8 Hz), 7.21-7.25 (m,
2 H), 7.49-7.53 (m, 1 H), 7.83-7.86 (m, 1 H); 13C NMR (125
MHz, DMSO-d6) δ 183.4, 172.6, 145.5, 142.1, 137.1, 133.0,
125.6, 124.1, 123.9, 120.2, 113.3, 111.0, 38.3, 29.2, 28.4, 28.0,
27.3, 26.7, 22.4 (2C), 11.4; MS m/ z 325 (M+ + 2), 323 (M+).
Anal. Calcd for C21H25NO2: C, 77.99; H, 7.79; N, 4.33.
Found: C, 78.03; H, 7.64; N, 4.41.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra of 3b-f (10 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
Ca r ba zoqu in ocin F (3f). The same procedure as above
was carried out by using 29d (92%): mp 229-231 °C (from
EtOAc) (lit.6 mp 208-210 °C); IR (KBr) 1639, 1624, 1464, 1250,
1
752 cm-1; H NMR (500 MHz, DMSO-d6) δ 0.83 (d, 6 H, J )
6.7 Hz), 1.10-1.17 (m, 2 H), 1.21-1.35 (m, 4 H), 1.42-1.61
J O962038T