Regioselective intramolecular reactions of 2-indolylacyl radicals with pyridines: A direct synthetic entry to ellipticine quinones

Article abstract of DOI:10.1021/jo0514974

2-Indolylacyl radicals generated from the corresponding selenoesters under hexabutylditin-hv conditions undergo regioselective intramolecular reaction with unprotonated pyridines to give polycyclic indolylpyridyl ketones. For substrates bearing a (3-pyridyl)methyl moiety connected to the 3-position of the indole ring, the cyclization provides easy access to ellipticine quinones.

Full text of DOI:10.1021/jo0514974

SCHEME 1
Regioselective Intramolecular Reactions of
2-Indolylacyl Radicals with Pyridines: A
Direct Synthetic Entry to Ellipticine
Quinones
M.-Llu¨ısa Bennasar,* Toma`s Roca, and
Francesc Ferrando
Laboratory of Organic Chemistry, Faculty of Pharmacy,
University of Barcelona, Barcelona 08028, Spain
bennasar@ub.edu
Received July 19, 2005
In the past few years, we have been studying the
generation of 2- and 3-indolylacyl radicals from the
corresponding phenyl selenoesters and their reactions
with alkene acceptors under reductive conditions.10 Our
interest in this area led us to envisage intramolecular
reactions of these radical intermediates with aromatic
rings as a general approach to polycyclic aryl indolyl
ketones, which are common substructures of many
natural and medicinal compounds.11 Thus, we have
recently reported how 2-indolylacyl radicals, such as
those derived from selenoesters 1 and 2 (Scheme 1),
undergo cyclization upon phenyl rings under nonreduc-
tive (hexabutylditin, hν) conditions.12 We believed that
the extension of the above reactions to analogous pyridine
substrates would be of interest, complementing the
classical protocol of Minisci for the homolytic acylation
of protonated pyridines under oxidative conditions,13
mainly developed in its intermolecular version.14 We
herein report our work on this subject presenting as the
2-Indolylacyl radicals generated from the corresponding
selenoesters under hexabutylditin-hν conditions undergo
regioselective intramolecular reaction with unprotonated
pyridines to give polycyclic indolylpyridyl ketones. For
substrates bearing a (3-pyridyl)methyl moiety connected to
the 3-position of the indole ring, the cyclization provides easy
access to ellipticine quinones.
Intramolecular reactions of nucleophilic carbon-cen-
tered radicals with aromatic systems are often of syn-
thetic value for the construction of polycyclic compounds
incorporating aromatic rings.1 Fully aromatic products
are generally obtained after the oxidation of the initially
formed cyclohexadienyl radical,2 which takes place even
under the most commonly used tributyltin hydride-
AIBN reductive conditions.3 In this context, cyclizations
of aryl and alkyl radicals upon heteroaromatic substrates
such as azoles,4 indoles,5,6 pyridines,7 or quinolines7a have
become increasingly important for the synthesis of oth-
erwise quite inaccessible substituted heterocycles. How-
ever, similar processes involving acyl radicals, which
have a high synthetic potential due to their intrinsic
functionalization,8 have scarcely been investigated.9
(5) For instance, see: (a) Kraus, G. A.; Kim, H. Synth. Commun.
1993, 23, 55-64. (b) Artis, D. R.; Cho, I.-S.; Jaime-Figueroa, S.;
Muchowski, J. M. J. Org. Chem. 1994, 59, 2456-2466. (c) Wang, S.-
F.; Chuang, C.-P. Tetrahedron Lett. 1997, 38, 7597-7598. (d) Moody,
C. J.; Norton, C. L. J. Chem. Soc., Perkin Trans. 1 1997, 2639-2643.
(e) Caddick, S.; Shering, C. L.; Wadman, S. N. Tetrahedron 2000, 56,
465-473. (f) Menes-Arzate, M.; Mart´ınez, R.; Cruz-Almanza, R.;
Muchowski, J. M.; Osornio, Y. M.; Miranda, L. D. J. Org. Chem. 2004,
69, 4001-4004.
(6) For the isolation of dihydro derivatives of indole, see: (a) Ziegler,
F. E.; Jeroncic, L. O. J. Org. Chem. 1991, 56, 3479-3486. (b) Gribble,
G. W.; Fraser, H. L.; Badenock, J. C. Chem. Commun. 2001, 805-
806. (c) Flanagan, S. R.; Harrowven, D. C.; Bradley, M. Tetrahedron
Lett. 2003, 44, 1795-1798.
(7) (a) Harrowven, D. C.; Sutton, B. J. In Progress in Heterocyclic
Chemistry; Gribble, G. W., Joule, J. A., Eds.; Elsevier: Amsterdam,
2004; Vol. 16, pp 27-53. For more recent work, see: (b) Bacque´, E.;
El Qacemi, M.; Zard, S. Z. Org. Lett. 2004, 6, 3671-3674. (c) Crich,
D.; Patel, M. Heterocycles 2004, 64, 499-504. (d) Nu´n˜ez, A.; Sa´nchez,
A.; Burgos, C.; Alvarez-Builla, J. Tetrahedron 2004, 60, 6217-6224.
(8) For reviews on acyl radicals, see: (a) Ryu, I.; Sonoda, N.; Curran,
D. P. Chem. Rev. 1996, 96, 177-194. (b) Chatgilialoglu, C.; Crich, D.;
Komatsu, M.; Ryu, I. Chem. Rev. 1999, 99, 1991-2069.
(9) For cyclization of acyl radicals upon indoles, see: (a) Miranda,
L. D.; Cruz-Almanza, R.; Pavo´n, M.; Alva, E.; Muchowski, J. M.
Tetrahedron Lett. 1999, 40, 7153-7157. Upon pyrroles, see: (b) Allin,
S. M.; Barton, W. R. S.; Bowman, W. R.; McInally, T. Tetrahedron Lett.
2001, 42, 7887-7890.
* Tel: 34 934 024 540. Fax: 34 934 024 539.
(1) Studer, A.; Bossart, M. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M. P., eds.; Wiley-VCH: Weinheim, Germany, 2001;
Vol. 2, pp 62-80.
(2) Crich, D.; Hwang, J.-T. J. Org. Chem. 1998, 63, 2765-2770.
(3) For a recent discussion, see: Beckwith, A. L. J.; Bowry, V. W.;
Bowman, W. R.; Mann, E.; Parr, J.; Storey, J. M. D. Angew. Chem.,
Int. Ed. 2004, 43, 95-98 and references therein.
(4) (a) Aldabbagh, F.; Bowman, W. R.; Mann, E.; Slawin, A. M. Z.
Tetrahedron 1999, 55, 8111-8128. (b) Escolano, C.; Jones, K. Tetra-
hedron 2002, 58, 1453-1464. (c) Allin, S. M.; Barton, W. R. S.;
Bowman, W. R.; McInally, T. Tetrahedron Lett. 2002, 43, 4191-4193.
(d) Gagosz, F.; Zard, S. Z. Org. Lett. 2002, 4, 4345-4348. (e) Allin, S.
M.; Bowman, W. R.; Elsegood, M. R. J.; McKee, V.; Karim, R.; Rahman,
S. S. Tetrahedron 2005, 61, 2689-2696. See also: (f) Bowman, W. R.;
Fletcher, A. J.; Potts, G. B. S. J. Chem. Soc., Perkin Trans. 1 2002,
2747-2762. (g) Crich, D.; Patel, M. Org. Lett. 2005, 7, 3625-3628.
(10) (a) Bennasar, M.-L.; Roca, T.; Griera, R.; Bosch, J. Org. Lett.
2001, 3, 1697-1700. (b) Bennasar, M.-L.; Roca, T.; Griera, R.; Bassa,
M.; Bosch, J. J. Org. Chem. 2002, 67, 6268-6271. (c) Bennasar, M.-
L.; Roca, T.; Ferrando, F. Org. Lett. 2004, 6, 759-762.
(11) Sundberg, R. J. Indoles; Academic Press: New York, 1996; pp
105-134.
(12) Bennasar, M.-L.; Roca, T.; Ferrando, F. Tetrahedron Lett. 2004,
45, 5605-5609.
10.1021/jo0514974 CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/04/2005
J. Org. Chem. 2005, 70, 9077-9080
9077

SCHEME 2a
FIGURE 1. Other reaction products.
SCHEME 3
ate acyl radical to aldehyde 10 (Figure 1) when sele-
noesters 4 and 6 were submitted to standard reductive
(n-Bu3SnH o (SiMe3)3SiH-AIBN) conditions. However,
the desired cyclization did take place upon treatment
with n-Bu6Sn2 (2 mol, 300 W sun lamp), although the
yields were lower than in the phenyl series. For sele-
noester 4, the acylation took place exclusively at the
4-position of the pyridine ring to give tetracycle 7, a
deoxoderivative of the known ellipticine precursor 9,17 in
35% yield. No trace of the regioisomeric product coming
from the alternative radical attack at the 2-position was
detected. This regiochemical outcome is noteworthy,
being in clear contrast with that observed in related
reactions involving aryl radicals, which usually provide
regioisomeric mixtures.7 On the other hand, the 2-in-
dolylacyl radical derived from selenoester 6 reacted at
the 3-position of the pyridine ring in a less efficient way,
ultimately leading to the overoxidized keto lactam 8, a
synthetic precursor of isoellipticine,18 in 15% yield. In
both cases, significant amounts (20-30%) of tin esters
11 (Figure 1) were also obtained.
The cyclization process can be understood by studying
the radical reactions depicted in Scheme 3 for selenoester
4. After cleavage of n-Bu6Sn2 under the influence of heat
and/or light, the resulting tributyltin radical generates
the 2-indolylacyl radical A, which reacts at the 4-position
of the pyridine ring to give the azacyclohexadienyl radical
B. Subsequent oxidation would lead to 7, probably by a
simple hydrogen abstraction19 by the peroxy radical
n-Bu3SnOO• coming from the reaction of tin radicals with
oxygen, which was not rigorously excluded from the
reaction mixture. A similar addition-rearomatization
mechanism followed by an additional oxidation at the
interannular methylene group could account for the
formation of keto lactam 8 from selenoester 6 (not
shown).
a Reagents and conditions: (a) NaH, THF, 3- or 4-(chlorometh-
yl)pyridine, HCl, rt, overnight, 70% (3), 65% (5); (b) 2 N KOH,
MeOH-dioxane, reflux, 2 h, then 2 N HCl; (c) Et3N, then PhSeCl,
PBu3, THF, rt, overnight, 82% (4), 83% (6); (d) n-Bu6Sn2, 300 W,
C6H6, reflux, 24 h, 35% (7), 15% (8).
most significant result a straightforward synthetic entry
to ellipticine quinones, which have an intrinsic interest
as antitumor agents,15 and are important intermediates
in the synthesis of ellipticines.16
Selenoesters 4 and 6, bearing 3- or 4-pyridylmethyl
moieties connected to the indole nitrogen, were selected
as substrates to study 2-indolylacyl radical cyclizations
leading to indolo[1,2-b]naphthyridinones (Scheme 2),
which constitute advanced intermediates in the earliest
Gribble syntheses of ellipticine and analogues.17,18 As
expected, these radical precursors were easily accessible
by N-alkylation of methyl indole-2-carboxylate with the
appropriate (chloromethyl)pyridine, followed by hydroly-
sis of the resulting methyl esters 3 and 5, and subsequent
phenylselenation.
In analogy to our previous results for selenoester 1,12
we observed only premature reduction of the intermedi-
(13) (a) Minisci, F.; Vismara, E.; Fontana, F. Heterocycles 1989, 28,
489-519. (b) Fontana, F.; Minisci, F.; Barbosa, M. C. N.; Vismara, E.
J. Org. Chem. 1991, 56, 2866-2869. (c) Minisci, F.; Recupero, F.;
Ceccheto, A.; Punta, C.; Gambarotti, C.; Fontana, F.; Pedulli, G. F. J.
Heterocycl. Chem. 2003, 40, 325-328. See also: (d) Nicolaou, K. C.;
Safina, B. S.; Funke, C.; Zak, M.; Ze´cri, F. J. Angew. Chem., Int. Ed.
2002, 41, 1937-1940.
(14) For an isolated example of the intramolecular version, see: Doll,
M. K.-H. J. Org. Chem. 1999, 64, 1372-1374.
(15) Bernardo, P. H.; Chai, C. L. L.; Heath, G. A.; Mahon, P. J.;
Smith, G. D.; Waring, P.; Wilkes, B. A. J. Med. Chem. 2004, 47, 4958-
4963.
(16) Kno¨lker, H.-J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303-4427
and references therein.
(17) (a) Saulnier, M. G.; Gribble, G. W. J. Org. Chem. 1982, 47,
2810-2812. (b) Gribble, G. W.; Saulnier, M. G.; Obaza-Nutaitis, J. A.;
Ketcha, D. M. J. Org. Chem. 1992, 57, 5891-5899.
(18) Saulnier, M. G.; Gribble, G. W. J. Org. Chem. 1983, 48, 2690-
2695.
The relative inefficiency of the above cyclizations with
respect to the phenyl series (Scheme 1) was somewhat
(19) For discussions, see: (a) Josien, H.; Ko, S.-B.; Bom, D.; Curran,
D. P. Chem.sEur. J. 1998, 4, 67-83. (b) Wang, C.; Russell, G. A.;
Trahanovsky, W. S. J. Org. Chem. 1998, 63, 9956-9959. (c) Miranda,
L. D.; Cruz-Almanza, R.; Pavo´n, M.; Romero, Y.; Muchowski, J. M.
Tetrahedron Lett. 2000, 41, 10181-10184. (d) Bowman, W. R.; Bridge,
C. F.; Cloonan, M. O.; Leach, D. C. Synlett 2001, 765-768.
9078 J. Org. Chem., Vol. 70, No. 22, 2005

SCHEME 4a
unexpected, as unprotonated pyridines have been re-
ported to exhibit reactivity profiles toward most nucleo-
philic carbon-centered radicals that are similar to ben-
zene derivatives.13a Nevertheless, these differences can
be attributed to the presence of pendant electron-
withdrawing 3- or, in particular, 4-pyridylmethyl moieties
at the indole nitrogen, which would diminish the reactiv-
ity of the intermediate acyl radical. This would lead to a
buildup of radical concentration, allowing undesired
secondary reactions such as conversion into tin ester 11
to take place.20
We next turned to radical precursors in which the
3-pyridylmethyl moiety was attached at the indole 3-po-
sition. In this series, the hope was that the reaction would
follow the same regiochemical course as described above
for selenoester 4, giving access to the pyrido[4,3-b]-
carbazole skeleton characteristic of the indole alkaloid
ellipticine. Considering that the substituent installed at
the indole nitrogen could modulate the reactivity of the
intermediate acyl radical and, consequently, determine
the efficiency of the process, we decided to study the
cyclization from a variety of N-substituted selenoesters
15a-d (Scheme 4, Table 1).
Their preparation was a bit more laborious than in the
above series, and required the use of 2,3-disubstituted
indoles 12 as the starting products. Thus, reaction of
12a-c with 3-pyridylmagnesium bromide, followed by
triethylsilane reduction of the resulting carbinols
13a-c, provided methyl esters 14a-c in acceptable
yields. N-(Methoxymethyl) ester 14d was prepared by
N-alkylation of the unsubstituted derivative 14c, as
triethylsilane reduction of carbinol 13 (R ) MOM)
resulted in the concomitant reduction of the N-substitu-
ent to give the N-methyl derivative 14a. Subsequent
hydrolysis of 14a-d, followed by phenylselenation of the
respective carboxylic acids, gave the target selenoesters
15a-d.
a Reagents and conditions: (a) 3-pyridylmagnesium bromide,
-40°C to room temperature, 12 h; (b) Et3SiH, TFA, rt, 7 h, 14a
(60%), 14b (55%), 14c (50%); (c) NaH, THF, MOMCl, 0 °C to room
temperature, 12 h, 85%; (d) LiOH, 3:1 THF/H2O, 65 °C, 5 h; (e)
Et3N, then PhSeCl, PBu3, THF, rt, overnight, 15a (80%), 15b
(76%), 15c (70%), 15d (80%); (f) n-Bu6Sn2, 300 W, C6H6, reflux,
24 h, see Table 1.
To our delight, 2-indolylacyl radicals derived from
N-methyl selenoesters 15a and 15b (entries 1 and 2)
efficiently underwent regioselective cyclization upon the
4-position of the pyridine ring and, after the in situ
oxidation at the interannular methylene group, gave the
known ellipticine quinones 16a21 and 16b21,22 in 60 and
42% yield, respectively. Only minor amounts of regio-
isomers 17a (5%) and 17b (8%) were formed. However,
the acyl radical derived from 15d (entry 4) displayed
diminished reactivity compared to that of those derived
from 15a and 15b, probably due to the presence of the
methoxymethyl group, which acts as an electron-with-
drawing moiety. Thus, quinone 16d21 was isolated in a
poor 10% yield along with trace amounts of the C-2
regioisomer 17d. Attempts to improve this result using
dicumyl peroxide5f were unsuccessful, as they led to the
recovery of the starting selenoester.
TABLE 1. n-Bu6Sn2-Mediated Radical Cyclization of
Selenoesters 15
ellipticine quinone
(yield, %)a
other products
(yield, %)a
entry
selenoester
1
2
3
4
15a
15b
15c
15d
16a (60)
16b (42)
17a (5), 18a (10)
17b (8)b
18c (85)
16d (10)
17d (2), 18dc
a Isolated yields. b Minor amounts of the product coming from
cyclization upon the benzene ring were also detected. c Not
isolated. Major product in the reaction mixture (6:1 with respect
to 16d + 17d).
Quite unexpectedly, cyclization did not occur for the
unsubstituted selenoester 15c (entry 3), indicating that
the radical reaction was somehow inhibited by the
presence of the indole NH group.23 In the last two cases,
it is somewhat significant that the undesired formation
of tin esters 18c,d, a minor process in the productive
series, was the predominant pathway.20
(20) Formation of tin esters 11 and 18 can be explained by the
reaction of the corresponding selenoesters with hexabutylditin oxide,
which would be formed in the reaction mixture on exposure of
hexabutylditin to light. Alternatively, they can be formed by reaction
of the selenoesters with hexabutylditin, followed by oxidation of the
resulting 2-indolylacyltin: Kosugi, M.; Naka, H.; Sano, H.; Migita, T.
Bull. Chem. Soc. Jpn. 1987, 60, 3462-3464.
(21) Watanabe, M.; Snieckus, V. J. Am. Chem. Soc. 1980, 102, 1457-
1460.
(22) Miki, Y.; Tada, Y.; Matsushita, K. Heterocycles 1998, 48, 1593-
1597.
As expected, ellipticine quinones 16a, 16b, and 16d
showed physical and spectroscopic data identical to those
(23) For the radical inhibitory properties of diphenylamine and other
aromatic amines, see: MacFaul, P. A.; Ingold, K. U.; Lusztyk, J. J.
Org. Chem. 1996, 61, 1316-1321.
J. Org. Chem, Vol. 70, No. 22, 2005 9079

6-Methyl-6H-pyrido[4,3-b]carbazole-5,11-dione (16a):21
60% yield; elution with 5:5 hexanes/AcOEt; mp 240-242 °C (lit.21
245 °C); 1H NMR (500 MHz, assignment aided by HSQC and
HMBC) δ 4.29 (s, 3H, NMe), 7.46 (ddd, J ) 1, 6.5, 8 Hz, 1H,
9-H), 7.51 (d, J ) 8.5 Hz, 1H, 7-H), 7.55 (ddd, J ) 1, 6.5, 8 Hz,
1H, 8-H), 7.98 (d, J ) 5 Hz, 1H, 4-H), 8.49 (d, J ) 8.5 Hz, 1H,
10-H), 9.05 (d, J ) 5 Hz, 1H, 3-H), 9.47 (s, 1H, 1-H); 13C NMR
(100.6 MHz, assignment aided by HSQC and HMBC) δ 32.2
(NMe), 111.1 (C-7), 118.7 (C-4), 119.4 (C-10b), 123.8 (C-10a),
124.3 (C-10), 125.3 (C-9), 126.6 (C-11a), 128.3 (C-8), 134.6 (C-
5a), 139.2 (C-4a), 140.5 (C-6a), 148.5 (C-1), 155.1 (C-3), 178.3
(C-5), 180.7 (C-11).
previously described.15,21,22 Because both 16b21,22,24 and
16d21 were transformed into ellipticine, the synthesis
reported here constitutes a formal synthesis of this
natural product.
In conclusion, we have shown that the cyclization of
2-indolylacyl radicals upon pyridines under n-Bu6Sn2-
hν conditions takes place with notable regioselectivity to
give tetracyclic indolyl 4-pyridyl ketones. The effective-
ness of this radical protocol is illustrated by a fast
synthetic entry to ellipticine quinones.
6-Benzyl-6H-pyrido[4,3-b]carbazole-5,11-dione (16b):21,22
42% yield; elution with 7:3 hexanes/AcOEt; mp 256-258 °C (lit.21
268 °C); 1H NMR (300 MHz) δ 6.00 (s, 2H), 7.18 (dd, J ) 1.8,
8.1 Hz, 2H), 7.29 (m, 3H), 7.42-7.52 (m, 3H), 7.94 (dd, J ) 0.6,
5.1 Hz, 1H), 8.52 (br d, J ) 7.8 Hz, 1H), 9.03 (d, J ) 5.1 Hz,
1H), 9.47 (s, 1H); 13C NMR (DMSO-d6, 100.6 MHz) δ 47.8 (CH2),
112.6 (CH), 118.2 (C), 118.6 (CH), 122.8 (CH), 123.0 (C), 125.1
(CH), 126.1 (C), 126.8 (CH), 127.6 (CH), 128.0 (CH), 128.7 (CH),
134.5 (C), 136.7 (C), 139.0 (C), 139.5 (C), 147.2 (CH), 155.2 (CH),
177.4 (C), 180.3 (C). Anal. Calcd for C22H14N2O2‚3/2H2O: C,
72.42; H, 4.69; N, 7.67. Found: C, 72.15; H, 4.33; N, 7.39.
6-(Methoxymethyl)-6H-pyrido[4,3-b]carbazole-5,11-di-
one (16d):15,21 10% yield; elution with 6:4 hexanes/AcOEt; mp
190-193 °C (lit.21 196-197 °C); 1H NMR (CDCl3, 200 MHz) δ
3.40 (s, 3H), 6.16 (s, 2H), 7.25-7.60 (m, 2H), 7.68 (d, J ) 8.6
Hz, 1H), 7.98 (d, J ) 4.8 Hz, 1H), 8.50 (d, J ) 8 Hz, 1H), 9.07
(d, J ) 5.2 Hz, 1H), 9.47 (s, 1H); 13C NMR (CDCl3, 100.6 MHz)
δ 56.6 (CH3), 75.4 (CH2), 112.0 (CH), 118.6 (CH), 120.3 (C), 123.8
(C), 124.1 (CH), 125.4 (CH), 126.0 (C), 128.7 (CH), 134.5 (C),
139.0 (C), 140.2 (C), 148.4 (CH), 155.1 (CH), 177.8 (C), 181.0
(C).
Experimental Section
General Procedure for the Radical Cyclization of Phen-
yl Selenoesters 4, 6, and 15. A solution of the appropriate
selenoester (0.50 mmol) and n-Bu6Sn2 (0.51 mL, 1 mmol) in C6H6
(30 mL) was refluxed under Ar under sun lamp irradiation (300
W) for 24 h. The solution was concentrated under reduced
pressure. The resulting residue was partitioned between hexanes
(15 mL) and acetonitrile (15 mL), and the polar layer was washed
with hexanes (3 × 15 mL). The solvent was removed, and the
crude product was purified by flash chromatography (SiO2). For
15b, the crude product was treated with a 0.5 M solution of KOH
in MeOH (10 mL) at room temperature for 2 h before the
chromatography. Yields, methods of purification, and NMR data
are given below.
12H-Indolo[1,2-b][2,7]naphthyridin-5-one (7): 35% yield;
elution with 99:1 CH2Cl2/MeOH; mp 190-192 °C; 1H NMR (500
MHz) δ 5.45 (s, 2H), 7.22 (ddd, J ) 1.5, 7, 8.5 Hz, 1H), 7.46 (m,
2H), 7.52 (s, 1H), 7.77 (dt, J ) 1, 1, 7 Hz, 1H), 8.08 (d, J ) 5 Hz,
1H), 8.79 (d, J ) 5 Hz, 1H), 8.89 (s, 1H); 13C NMR (CDCl3, 75.4
MHz) δ 42.2 (CH2), 107.3 (CH), 110.2 (CH), 119.3 (CH), 122.0
(CH), 123.7 (CH), 126.5 (CH), 127.2 (C), 129.9 (C), 132.0 (C),
136.2 (C), 137.7 (C), 148.8 (CH), 149.6 (CH), 175.9 (C); HRMS
calcd for C15H10N2O 234.0793, found 234.0798.
Acknowledgment. Financial support from the
Ministerio de Ciencia y Tecnolog´ıa (MCYT-FEDER,
Spain) through Project BQU2003-04967-C-02-02 is grate-
fully acknowledged. We also thank the DURSI (Gener-
alitat de Catalunya) for Grant 2001SGR00084. F.F.
thanks the University of Barcelona for a grant.
Indolo[1,2-b][2,6]naphthyridin-5,12-dione (8):17 15% yield;
elution with 99:1 CH2Cl2/MeOH; H NMR (200 MHz) δ 7.43 (t,
1
J ) 8 Hz, 1H), 7.64 (t, J ) 8.4 Hz, 1H), 7.73 (s, 1H), 7.78 (d, J
) 8 Hz, 1H), 8.25 (d, J ) 5.2 Hz, 1H), 8.62 (d, J ) 8.4 Hz, 1H),
9.13 (d, J ) 5 Hz, 1H), 9.55 (s, 1H); 13C NMR (CDCl3, 75.4 MHz)
δ 117.2 (CH), 117.4 (CH), 121.3 (CH), 124.1 (CH), 125.9 (CH),
126.5 (C), 128.6 (C), 130.4 (CH), 133.1 (C), 137.1 (C), 137.4 (C),
149.3 (CH), 155.5 (CH), 157.7 (C), 174.7 (C); HRMS calcd for
Supporting Information Available: General experimen-
tal protocols and detailed experimental procedures for the
preparation of all synthetic intermediates. Characterization
data of new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
C
15H8N2O2 248.0586, found 248.0596.
(24) Yokoyama, Y.; Okuyama, N.; Iwadate, S.; Momoi, T.; Murakami,
Y. J. Chem. Soc., Perkin Trans. 1 1990, 1319-1329.
JO0514974
9080 J. Org. Chem., Vol. 70, No. 22, 2005