Regiochemical switching in Diels-Alder cycloadditions by change in oxidation state of removable diene sulfur substituents. Synthesis of carbazoles by sequential heteroannulation and Diels-Alder cycloaddition

Article abstract of DOI:10.1021/jo0268714

The palladium-catalyzed heteroannulation of N-carbobenzyloxy-o-iodoanilines with 1-phenylthio-1,3-butadiene afforded indolines 7, which were oxidized with DDQ to produce vinylogous 2-(phenylthio)indoles 8. The latter compounds underwent highly regioselect

Full text of DOI:10.1021/jo0268714

SCHEME 1
Regioch em ica l Sw itch in g in Diels-Ald er
Cycloa d d ition s by Ch a n ge in Oxid a tion
Sta te of Rem ova ble Dien e Su lfu r
Su bstitu en ts. Syn th esis of Ca r ba zoles by
Sequ en tia l Heter oa n n u la tion a n d
Diels-Ald er Cycloa d d ition
Thomas G. Back,* Aleksandra Pandyra, and
J eremy E. Wulff
Department of Chemistry, University of Calgary,
Calgary, Alberta, Canada T2N 1N4
tgback@ucalgary.ca
Received December 18, 2002
Abstr a ct: The palladium-catalyzed heteroannulation of
N-carbobenzyloxy-o-iodoanilines with 1-phenylthio-1,3-buta-
diene afforded indolines 7, which were oxidized with DDQ
to produce vinylogous 2-(phenylthio)indoles 8. The latter
compounds underwent highly regioselective Diels-Alder
cycloadditions with methyl propiolate in the presence of
MeAlCl2 or AlCl3, with simultaneous elimination of ben-
zenethiol, to afford methyl N-(carbobenzyloxy)carbazole-3-
carboxylates 9 and, in some cases, the N-deprotected de-
rivatives 11. This is the opposite regiochemistry of that
observed previously with the corresponding sulfone ana-
logues of 8. Thus, the regiochemistry of the cycloaddition
can be effectively controlled by appropriate choice of oxida-
tion state of the diene sulfur substituent.
SCHEME 2
We recently reported1 that the palladium-catalyzed
heteroannulation2 of o-iodoanilines 1 with dienyl sulfones
23 affords the corresponding vinylogous 2-sulfonylindo-
lines 3, followed by further oxidation to the corresponding
indoles 4. The latter compounds undergo highly regiose-
lective Diels-Alder reactions to afford dihydrocarbazoles
or carbazoles 5 after elimination of the sulfone moiety
(Scheme 1).1 This approach provides a convenient route
to 4-substituted carbazole derivatives but fails for the
corresponding 3-substituted regioisomers. Since many
biologically interesting carbazoles4 are substituted at the
3-position, we were interested in finding a method for
switching the regiochemistry of the cycloaddition reaction
in order to render the latter isomers accessible.
regiochemistry.5 We now report that the palladium-
catalyzed heteroannulations of 1 with dienyl sulfide 6
proceed smoothly, as do the subsequent oxidations of the
products 7 with DDQ to afford 8 (Scheme 2). The
heteroannulations with dienyl sulfones 2 were typically
performed at room temperature in aqueous DMF con-
taining potassium carbonate in the presence of a catalytic
amount of palladium(II) acetate.1 Similar conditions were
employed in the preparation of 7, except that the use of
refluxing acetonitrile afforded superior yields to aqueous
Since the sulfone substituents in 4 are electron-
withdrawing, we reasoned that the corresponding sulfide
analogues 8, where the sulfur moiety is electron-donat-
ing, might undergo cycloadditions with the opposite
(4) For selected reviews of carbazoles, see: (a) Moody, C. J . Synlett
1994, 681. (b) Misra, N.; Luthra, R.; Singh, K. L.; Kumar, S. In
Comprehensive Natural Products Chemistry; Kelly, J . W., Ed.; Elsevi-
er: Amsterdam, 1999; Vol. 4, p 54. (c) Chakraborty, D. P. In Progress
in the Chemistry of Organic Natural Products; Herz, W., Grisebach,
H., Kirby, G. W., Eds.; Springer-Verlag: Wien, 1977; Vol. 34, pp 299-
371. (d) Bhattacharyya, P.; Chakraborty, D. P. In Progress in the
Chemistry of Organic Natural Products; Herz, W., Grisebach, H., Kirby,
G. W., Tamm, C., Eds.; Springer-Verlag: Wien, 1987; Vol. 52, pp 159-
209. (e) Chakraborty, D. P.; Roy, S. In Progress in the Chemistry of
Organic Natural Products; Herz, W., Kirby, G. W., Steglich, G. W.,
Tamm, C., Eds.; Springer-Verlag: Wien, 1991; Vol. 57, pp 71-152.
(5) For the effects of electron-withdrawing/donating substituents on
the regiochemistry of Diels-Alder reactions, see: Fleming, I. Frontier
Orbitals and Organic Chemical Reactions; Wiley: Chichester, UK,
1976; Chapter 4.
* To whom correspondence should be addressed. Phone: (403) 220-
6256. Fax: (403) 289-9488.
(1) Back, T. G.; Bethell, R. J .; Parvez, M.; Taylor, J . A. J . Org. Chem.
2001, 66, 8599.
(2) For other examples of nitrogen heterocycles prepared by het-
eroannulation of aryl halides with dienes, see: (a) 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.
(3) For a review of dienyl sulfones, see: Ba¨ckvall, J . E.; Chinchilla,
R.; Na´jera, C.; Yus, M. Chem. Rev. 1998, 98, 2291.
10.1021/jo0268714 CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/18/2003
J . Org. Chem. 2003, 68, 3299-3302
3299

SCHEME 3
3). The deprotection of 9a to 11a was also achieved in
excellent yield by hydrogenolysis (Scheme 3). Carbazole
11a is found in extracts of the roots of the ornamental
tree Clausena lansium,7 which are used in Taiwanese folk
medicine for the treatment of bronchitis and malaria.
Similar results were obtained with indoles 8b and 8c,
as shown in Scheme 3. In each case, only the correspond-
ing 3-substituted regioisomers 9b, 9c, and 11c were
detected. The 6-methyl derivative 9b was produced
rapidly at 0 °C in the presence of AlCl3 in dichloro-
methane, with no accompanying formation of the corre-
sponding free carbazole 11b. On the other hand, the
MeAlCl2 catalyst in toluene proved to be more effective
for the cyclization of diester 8c, which required a full day
at room temperature for optimum results and afforded
chiefly the deprotected carbazole 11c. Deprotection of
benzyl esters and related compounds is known to occur
with AlCl3 in anisole,8 an electron-rich arene. It is
therefore not surprising that similar deprotection oc-
curred in the case of 9a and 9c in the presence of MeAlCl2
in toluene but was not observed in the case of 9b, where
dichloromethane was employed as the solvent. In general,
at least 1 equiv of the Lewis acid was required for
optimum results, presumably because of its subsequent
reaction with the byproduct benzenethiol. As expected,
the more electron-rich indoles 8a and 8b reacted more
rapidly than the electron-deficient ester derivative 8c.
However, the latter indole afforded a higher cycloaddition
yield than 8a or 8b.
In conclusion, vinylogous 2-(phenylthio)indoles 8 can
be conveniently prepared in two steps by the palladium-
catalyzed heteroannulation of o-iodoanilines with dienyl
sulfide 6, followed by DDQ oxidation. The Lewis acid-
catalyzed Diels-Alder cycloadditions of 8 with methyl
propiolate afforded moderate yields of single regioisomers
of the corresponding cycloadducts 9 and 11, in which the
propiolate ester moiety is incorporated into the 3-position.
The protocol can be applied to carbazoles that are
unsubstituted (series a ) or that contain electron-donating
(series b) or -withdrawing (series c) substituents at C-6.
This method is complementary to the previously de-
scribed cycloadditions of the sulfone analogues of 8, which
result in exclusive formation of the 4-substituted regio-
isomers. Together, the two methods therefore provide
concise routes to a variety of 3,6- and 4,6-disubstituted
carbazoles and provide an interesting example of how a
complete reversal of regiochemistry can be achieved in
Diels-Alder reactions by changing the oxidation state
of a sulfur substituent in the diene reactant. This
strategy may find broader application in the regiocontrol
of other cycloadditions.
DMF. A 2-fold excess of dienyl sulfide 6 was employed
to compensate for its partial polymerization during the
reaction. The DDQ oxidations6 of 7 to 8 were performed
in refluxing toluene, and slightly higher yields were
generally obtained when the reactions were stopped prior
to the complete consumption of indolines 7a and 7b. The
yields of 8a and 8b in Scheme 2 are therefore based on
the recovery of small amounts of starting materials.
These results indicate that the sulfide moiety does not
interfere significantly with either the palladium-cata-
lyzed coupling step or the subsequent DDQ oxidation.
Moreover, both reactions tolerate electron-donating (se-
ries b) and -withdrawing (series c) groups in the para
position of the aniline and the 6-position of the resulting
indoline.
The Diels-Alder reactions of indoles 8 with methyl
propiolate were then investigated. When 8a was refluxed
in toluene with an excess of the dienophile in the absence
of a Lewis acid, a slow cycloaddition was observed, along
with concomitant elimination of benzenethiol, to afford
the two regioisomeric carbazoles 9a and 10a in 45% yield
in a ratio of 2:1 (Scheme 3). This indicated that replace-
ment of the sulfone moiety in 4 by the sulfide substituent
in 8a had indeed reversed the regioselectivity of the
reaction, as desired. Dramatic improvements in the
reaction rate and regioselectivity, along with modestly
enhanced yields, were observed in the presence of certain
Lewis acids, with AlCl3 and MeAlCl2 affording the best
results of several studied. Thus, in the presence of 1 equiv
of MeAlCl2, 8a reacted rapidly with excess methyl pro-
piolate in toluene at 0 °C to afford 9a as the sole
regioisomer, along with the deprotected carbazole 11a ,
isolated in yields of 45 and 17%, respectively (Scheme
Exp er im en ta l Section
Gen er a l Meth od s. All reagents, unless otherwise noted, were
obtained from commercial sources and purified by standard
methods as necessary. N-Cbz-o-iodonilines 1a -c were prepared
as described previously,1 and 1-phenylthio-1,3-butadiene (6)9 was
prepared by a literature procedure. Chromatography refers to
(7) Li, W.-S.; McChesney, J . D.; El-Feraly, F. S. Phytochemistry
1991, 30, 343.
(8) Tsuji, T.; Kataoka, T.; Yoshioka, M.; Sendo, Y.; Nishitani, Y.;
Hirai, S.; Maeda, T.; Nagata, W. Tetrahedron Lett. 1979, 2793.
(9) Hopkins, P. B.; Fuchs, P. L. J . Org. Chem. 1978, 43, 1208.
(6) Braude, E. A.; Brook, A. G.; Linstead, R. P. J . Chem. Soc. 1954,
3569.
3300 J . Org. Chem., Vol. 68, No. 8, 2003

flash chromatography on silica gel (230-400 mesh). NMR
spectra were recorded in deuteriochloroform unless otherwise
indicated.
21.2; MS (EI) m/z (%) 399 (M+, 2), 248 (58), 230 (83), 186 (100);
HRMS calcd for C25H21NO2S 399.1293, found 399.1264. Anal.
Calcd for C25H21NO2S: C, 75.16; H, 5.30; N, 3.51. Found: C,
75.05; H, 5.69; N, 3.65.
N-(Ca r boben zyloxy)-2-[(E)-2-(p h en ylth io)eth en yl]in d o-
lin e (7a ). N-Cbz-2-Iodoaniline (834 mg, 2.35 mmol), 1-phe-
nylthio-1,3-butadiene (773 mg, 4.77 mmol), finely ground K2CO3
(328 mg, 2.38 mmol), tetrabutylammonium bromide (766 mg,
2.38 mmol), and 85 mg (0.38 mmol) of Pd(OAc)2 were refluxed
in 50 mL of acetonitrile for 24 h. The mixture was diluted with
chloroform, filtered through Celite, and concentrated in vacuo.
The crude product was chromatographed (hexanes/ethyl acetate,
13:1) to afford 599 mg (66%) of 7a as a light yellow oil: IR (film)
Met h yl N-(Ca r b ob en zyloxy)-2-[(E)-2-(p h en ylt h io)et h -
en yl]in d ole-6-ca r boxyla te (8c). Product 8c was prepared in
86% yield by the same procedure as 8a , except that refluxing
was continued for 12 h and 1.1 equiv of DDQ was employed:
white solid, mp 94-96 °C (from ethanol); IR (film) 1737, 1713,
1582, 1306 cm-1 1H NMR (200 MHz) δ 8.25-8.07 (m, 2 H),
;
8.01-7.86 m, 1 H), 7.56-7.14 (m, 11 H), 6.92 (d, J ) 15.4 Hz, 1
H), 6.74 (s, 1 H), 5.48, (s, 2 H), 3.94, (s, 3 H); 13C NMR (50 MHz)
δ 167.2, 151.3, 139.4, 139.2 134.5, 134.3, 130.5, 129.2, 129.1,
128.8, 128.6, 127.9, 127.4, 125.7, 125.3, 122.4, 121.6, 115.5, 107.4,
69.3, 52.0; MS (EI) m/z (%) 443 (M+, 4), 248 (100), 91 (53); HRMS
calcd for C26H21NO4S 443.1191, found 443.1183. Anal. Calcd for
1
1706, 1602, 1482 cm-1; H NMR (200 MHz) δ 7.90-7.67 (m, 1
H), 7.49-7.11 (m, 12 H), 7.06-6.91 (m, 1 H), 6.36 (d, J ) 14.0
Hz, 1 H), 5.83 (dd, J ) 15.1, 7.7 Hz, 1 H), 5.29 (s, 2 H), 5.14-
4.97 (m, 1 H), 3.46 (dd, J ) 16.5, 9.9 Hz, 1 H), 2.85 (dd, J )
16.3, 2.7 Hz, 1 H); 13C NMR (50 MHz) δ 152.9, 141.5, 136.1,
134.8, 131.2, 129.6, 129.3, 129.0, 128.6, 128.1, 128.1, 127.7, 126.8,
125.4, 124.9, 123.0, 115.3, 67.3, 60.8, 34.9; MS (EI) m/z (%) 387
(M+, 3), 278 (33), 142 (86), 91 (72), 89 (100); HRMS calcd for
C24H21NO2S 387.1293, found 387.1304.
C
26H21NO4S: C, 70.41; H, 4.77; N, 3.16. Found: C, 70.31; H,
4.55; N, 3.14.
Meth yl N-(Car boben zyloxy)car bazole-3-car boxylate (9a)
a n d Met h yl Ca r b a zole-3-ca r b oxyla t e (11a ). A solution of
indole 8a (100 mg, 0.26 mmol) in 2 mL of toluene was added
dropwise over 5 min to a solution of methyl propiolate (0.23 mL,
2.6 mmol) and MeAlCl2 (0.26 mmol) in 5 mL of toluene at 0 °C.
The mixture was stirred for 20 min at room temperature. It was
then diluted with dichloromethane, washed with 10% HCl
solution, dried, and concentrated in vacuo. Chromatography
(hexanes/ethyl acetate, 10:1) afforded 42 mg (45%) of 9a and 10
mg (17%) of 11a .
N-(Ca r boben zyloxy)-6-m eth yl-2-[(E)-2-(p h en ylth io)eth -
en yl]in d olin e (7b). Product 7b was prepared in 75% yield by
the same procedure as 7a , except that refluxing was continued
for 4 days: colorless oil; IR (film) 1700, 1613, 1493 cm-1; 1H NMR
(200 MHz) δ 7.48-7.18 (m, 11 H), 7.00 (m, 2 H), 6.35 (d, J )
15.0 Hz, 1 H), 5.82 (dd, J ) 15.0, 7.5 Hz, 1 H), 5.28 (s, 2 H), 5.03
(m, 1 H), 3.43 (dd, J ) 16.0, 10.3 Hz, 1 H), 2.80 (dd, J ) 16.2,
2.4 Hz, 1 H), 2.30 (s, 3 H, Me); 13C NMR (50 MHz) δ 152.9, 139.2
136.2, 134.8, 132.6, 131.4, 129.6, 129.0, 128.6, 128.1, 128.0, 126.8,
125.6, 125.2, 115.0, 67.3, 60.9, 34.9, 20.9; MS (EI) m/z (%) 401
(M+, 2), 292 (16), 156 (100), 130 (73), 91 (48); HRMS calcd for
Ca r ba zole 9a : white solid, mp 131-134 °C (from ethanol);
IR (film) 1733, 1716, 1433, 1245 cm-1 1H NMR (200 MHz) δ
;
8.68 (dd, J ) 1.2, 0.6 Hz, 1 H), 8.33 (t, J ) 9.4 Hz, 2 H), 8.15
(dd, J ) 8.8, 1.8 Hz, 1 H), 8.05 (m, 1 H), 7.60-7.39 (m, 7 H),
5.60 (s, 2 H), 3.99 (s, 3 H); 13C NMR (50 MHz) δ 167.0, 152.0,
141.1, 138.7, 134.8, 128.8, 128.8, 128.6, 127.8, 126.0, 125.4, 125.3,
123.8, 121.5, 119.9, 116.4, 116.0, 69.1, 52.1; MS (EI) m/z (%) 359
C
25H23NO2S 401.1450, found 401.1463.
Met h yl N-(Ca r b ob en zyloxy)-2-[(E)-2-(p h en ylt h io)et h -
en yl]in d olin e-6-ca r boxyla te (7c). Product 7c was prepared
in 49% by the same procedure as 7a , except that refluxing was
continued for 8 days: yellow solid, mp 102-103 °C (from
(M+, 0.6), 315 (17), 164 (82), 91 (100); HRMS calcd for C22H17
-
NO4 359.1158, found 359.1127. Anal. Calcd for C22H17NO4: C,
73.53; H, 4.77; N, 3.90. Found: C, 73.07; H, 4.43; N 3.76.
Ca r ba zole 11a : mp 175-180 °C (lit.7 168-170 °C); 1H and
13C NMR spectra were in close agreement with those reported
in the literature.7
When the reaction was performed in refluxing toluene for 4
days in the presence of 10 mol % 2,6-di-tert-butyl-4-methylphenol
in the absence of the Lewis acid, carbazoles 9a (see above) and
10a (identical to an authentic sample1) were obtained in yields
of 30 and 15%, respectively.
1
ethanol); IR (film) 1717, 1613, 1487, 1258 cm-1; H NMR (200
MHz) δ 7.99-7.81 (m, 3 H) 7.55-7.26 (m, 10 H), 6.36 (d, J )
15.0 Hz, 1 H), 5.77 (dd, J ) 15.0, 7.6 Hz, 1H), 5.29 (s, 2 H),
5.15-5.01 (m, 1 H), 3.89 (s, 3 H), 3.46 (dd, J ) 16.2, 10.1 Hz, 1
H), 2.88 (dd, J ) 16.4, 2.6 Hz, 1 H); 13C NMR (100 MHz) δ 166.7,
152.7, 135.7, 134.4, 130.3, 130.0, 129.9, 129.6, 129.1, 128.6, 128.3,
128.2, 127.0, 126.4, 126.3, 124.8, 114.6, 67.7, 61.4, 51.9, 34.4;
MS (EI) m/z (%) 445 (M+, 3), 292 (51), 91 (100); HRMS calcd for
C26H23NO4S 445.1348, found 445.1368. Anal. Calcd for C26H23
-
NO4S: C, 70.09; H, 5.20; N, 3.14. Found: C, 69.90; H, 5.23; N,
2.91.
Met h yl N-(Ca r b ob en zyloxy)-6-m et h ylca r b a zole-3-ca r -
boxyla te (9b). A solution of indole 8b (51.7 mg, 0.129 mmol)
in 2 mL of CH2Cl2 was added via cannula to a stirred suspension
of methyl propiolate (0.10 mL, 1.1 mmol) and AlCl3 (35 mg, 0.26
mmol) in 1 mL of CH2Cl2 at 0 °C. The deep red reaction mixture
was stirred for 15 min at 0 °C, filtered through Celite, and
concentrated in vacuo. The crude product was immediately
chromatographed (hexanes/ethyl acetate, from 20:1 to 9:1) to
afford 27.5 mg (57%) of 9b as a white solid, mp 128-129.5 °C
(from ethanol): IR (film) 1732, 1714, 1608, 1387 cm-1; 1H NMR
(200 MHz) δ 8.65 (d, J ) 1.7 Hz, 1 H), 8.33 (d, J ) 8.7 Hz, 1 H),
8.16 (d, J ) 8.7 Hz, 1 H), 8.13 (dd, J ) 8.8, 1.7 Hz, 1 H), 7.84 (s,
1 H), 7.62-7.28 (m, 6 H), 5.58 (s, 2 H), 3.99 (s, 3 H), 2.52 (s, 3
H); 13C NMR (100 MHz) δ 167.1, 152.0, 141.3, 136.8, 134.9, 133.5,
129.0, 128.9, 128.8, 128.6, 128.5, 126.0, 125.6, 125.2, 121.5, 120.1,
116.1, 116.0, 69.0, 52.1, 21.3; MS (EI) m/z (%) 373 (M+, 0.6), 328
(47), 177 (93), 91 (100); HRMS calcd for C23H19NO4 373.1314,
found 373.1320. Anal. Calcd for C23H19NO4: C, 73.98; H, 5.13;
N, 3.75. Found: C, 74.30; H, 5.05; N, 3.80.
Dim eth yl N-(Ca r boben zyloxy)ca r ba zole-3,6-d ica r boxy-
la te (9c) a n d Dim eth yl Ca r ba zole-3,6-d ica r boxyla te (11c).
A solution of indole 8d (100 mg, 0.23 mmol) in 2 mL of toluene
was added dropwise over 5 min to a solution of methyl propiolate
(0.21 mL, 2.3 mmol) and MeAlCl2 (0.23 mmol) in 5 mL of toluene
at 0 °C. The mixture was then warmed to room temperature
and stirred for an additional 24 h. It was worked up as in the
preparation of 9a and 11a . Chromatography (hexanes/ethyl
N -(C a r b o b e n zy lo x y )-2-[(E )-2-(p h e n y lt h io )e t h e n y l]-
in d ole (8a ). A solution of DDQ (0.82 g, 3.6 mmol) in 25 mL of
toluene was added to indoline 7a (1.40 g, 3.6 mmol) in 75 mL of
toluene, and the solution was refluxed for 24 h. The mixture
was concentrated in vacuo, and chromatography of the residue
(hexanes/ethyl acetate, 10:1) afforded 226 mg (16%) of unreacted
7a and 0.82 g (71%, based on recovered 7a ) of 8a as a beige solid,
mp 85.5 °C (from ethyl acetate-hexanes): IR (film) 1733, 1580,
1449, 1323 cm-1 1H NMR (200 MHz) δ 8.15-8.06 (m, 1 H),
;
7.57-7.21 (m, 14 H), 6.88 (d, J ) 15.4 Hz, 1 H), 6.71 (s, 1 H),
5.48 (s, 2 H); 13C (50 MHz) δ 151.6, 138.0, 136.6, 134.9, 134.8,
130.1, 129.3, 129.2, 128.8, 128.7, 128.4, 127.1, 126.4, 124.5, 123.3,
122.8, 120.3, 115.8, 107.5, 68.9; MS (EI) m/z (%) 385 (M+, 2),
249 (100), 217 (87); HRMS calcd for C24H19NO2S 385.1137, found
385.1124. Anal. Calcd for C24H19NO2S: C, 74.78; H, 4.97; N, 3.63.
Found: C, 74.47; H, 4.91; N, 3.57
N-(Ca r boben zyloxy)-6-m eth yl-2-[(E)-2-(p h en ylth io)eth -
en yl]in d ole (8b). Product 8b was prepared in 71% yield (based
on 17% recovery of 7b) by the same procedure as 8a , except that
refluxing was continued for 8 h: white solid, mp 102 °C (from
ethyl acetate/hexanes); IR (film) 1724, 1652, 1397, 1337 cm-1
;
1H NMR (200 MHz) δ 7.96 (d, J ) 8.6 Hz, 1 H), 7.57-7.23 (m,
12 H), 7.06 (dd, J ) 8.7, 0.5 Hz, 1 H), 6.86 (d, J ) 15.2 Hz, 1 H),
6.64 (s, 1 H), 5.46 (s, 2 H), 2.41 (s, 3 H); 13C NMR (100 MHz) δ
151.7, 138.1, 135.0, 134.9, 134.8, 132.8, 130.1, 129.6, 129.2, 128.8,
128.6, 128.4, 127.1, 126.1, 125.9, 123.0, 120.2, 115.5, 107.3, 68.7,
J . Org. Chem, Vol. 68, No. 8, 2003 3301

acetate, 7:1, and then ethyl acetate) yielded 6 mg (6%) of 9c and
44 mg (69%) of 11c.
methanol/dichloromethane (5:1); 10% Pd on carbon (65 mg) was
added, and the mixture was stirred for 2 days under hydrogen
(1 atm). The mixture was filtered through Celite, and the filtrate
was concentrated in vacuo to provide a beige solid, which was
washed with hexanes (4 mL) to afford 7.2 mg (91%) of 11a as
an off-white solid with spectra identical to those of the sample
prepared from the cycloaddition of 8a .
Ca r ba zole 9c: mp 196.5-198 (from ethanol); IR (film) 1733,
1718, 1266 cm-1 1H NMR (200 MHz) δ 8.75 (dd, J ) 1.8, 0.6
;
Hz, 2 H), 8.36 (dd, J ) 8.8, 0.6 Hz, 2 H), 8.20 (dd, J ) 8.8, 1.7
Hz, 2 H), 7.63-7.51 (m, 2 H), 7.50-7.42 (m, 3 H), 5.61 (s, 2 H),
4.00 (s, 6 H); 13C NMR (50 MHz) δ 166.8, 141.5, 129.2, 129.0,
128.9, 128.7, 128.2, 125.8, 125.4, 121.8, 116.1, 69.4, 52.2; MS
(EI) m/z (%) 417 (M+, 0.5), 373 (12), 254 (18), 164 (40), 91 (100);
HRMS calcd for C24H19NO6 417.1212, found 417.1252.
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada (NSERC)
for financial support. J .E.W. thanks NSERC and the
Alberta Heritage Foundation for Medical Research
(AHFMR) for Graduate Scholarships. A.P. thanks AH-
FMR and Pfizer, Inc., for Summer Studentships.
Ca r ba zole 11c:10 IR (film) 1706, 1692, 1629, 1603, 1587,
1
1325, 1242, 1105, 767 cm-1; H NMR (400 MHz, acetone-d6) δ
8.93 (dd, J ) 1.6, 0.6 Hz, 2 H), 8.12 (dd, J ) 8.6, 1.7 Hz, 2 H),
7.64 (dd, J ) 8.6, 0.6 Hz, 2 H), 3.93 (s, 6 H); 13C NMR (100 MHz,
acetone-d6) δ 166.8, 143.5, 127.7, 122.9, 122.7, 122.0, 111.1, 51.2;
MS (EI) m/z (%) 283 (M+, 4), 252 (20), 164 (100); HRMS calcd
for C16H13NO4 283.0845, found 283.0833.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of new compounds and of carbazoles 11a and 11c. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Dep r otection of Ca r ba zole 9a to Ca r ba zole 11a . Carba-
zole 9a (12.6 mg, 0.0351 mmol) was dissolved in 30 mL of
(10) Negodyaev, N. D.; Pushkareva, Z. V. Khim. Geterotsikl. Soedin.
1967, 60; Chem. Abstr. 1969, 70, 87443.
J O0268714
3302 J . Org. Chem., Vol. 68, No. 8, 2003