Synthesis and reactivity of a novel class of long-lived ammonium ylides: Derivatives of benzo[b]pyrrolo[2,1-f][1.6]naphthyridine

Article abstract of DOI:10.1021/jo8003698

(Chemical Equation Presented) Reaction of 10-cyanotetrahydrobenzo[b][1,6] naphthyridines (1-6) with activated alkynes affords stable benzo[b]pyrrolo[2,1- f][1,6]naphthyridine-4-ium ylides (7-14) in moderate yields. A proposed mechanism for their formation consists of a new tandem multistage process.

Full text of DOI:10.1021/jo8003698

Synthesis and Reactivity of a Novel Class of Long-Lived Ammonium
Ylides: Derivatives of Benzo[b]pyrrolo[2,1-f][1.6]naphthyridine
Leonid G. Voskressensky,* Ilya V. Vorobiev, Tatyana N. Borisova, and
Alexey V. Varlamov
Organic Chemistry Department of the Russian Peoples Friendship UniVersity, 6 Miklukho-Maklaya St.,
Moscow, Russia, 117198
lVoskressensky@sci.pfu.edu.ru
ReceiVed February 21, 2008
Reaction of 10-cyanotetrahydrobenzo[b][1,6]naphthyridines (1-6) with activated alkynes affords stable
benzo[b]pyrrolo[2,1-f][1,6]naphthyridine-4-ium ylides (7-14) in moderate yields. A proposed mechanism
for their formation consists of a new tandem multistage process.
Introduction
propiolate and dimethylacetylene dicarboxylate (DMAD). We
have previously reported 8on the transformations of compounds
1 and 2 under the action of DMAD in methanol at room
temperature. It was demonstrated that they undergo addition of
the DMAD molecule, followed by Stevens rearrangement of
the intermediate ylide, yielding methyl dioates A. The alternative
transformation sequence starts with the migration of dimethyl
butene dioate anion to the carbon of CN group, followed by
the addition of 1 mol of water, thus providing succinates B
(Scheme 1). We have also registered (in the case of 1) the
formation of a small amount of a deeply red colored byproduct,
to which we were unable to assign a structure. Later on we
elucidated the structure of this byproduct, a representative of a
new class of long-lived ammonium ylides, and optimized the
reaction conditions for its synthesis.
Tandem reactions provide an opportunity for linking the
synthetic power of two or more transformations in a single
operation.1,2 These reactions are among the most powerful
building tools available because they rapidly increase the
complexity of a substrate starting from relatively simple
precursors.3,4 Michael addition is one of the most common
reaction steps in different tandem transformations.5,6
As a consequence of our continuing interest in the develop-
ment of tandem transformations of heteroannulated tetrahydro-
pyridines under the action of activated alkynes,7 we studied the
reaction of tetrahydrobenzonaphthyridines 1-6 with methyl
(1) Ho, T. L. In Tandem Organic Reactions; Wiley-Interscience: New York,
1992.
(2) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. 1993, 32, 31.
(3) Ziegler, F. E. In ComprehensiVe Organic Synthesis; Paquette, L. A. Ed.;
Pergamon Press: Oxford, 1991; Vol. 5, Chapter 7, p 3.
(4) (a) Tsuge, O.; Kanemasa, S.; Takenaka, S. Bull. Chem. Soc. Jpn. 1983,
56, 2073. (b) Tsuge, O.; Kanemasa, S.; Takenaka, S. Chem. Lett. 1983, 519. (c)
Curran, D. P. Synlett 1991, 63.
In this Article, we would like to report effective syntheses
of benzo[b]pyrrolo[2,1-f][1,6] naphthyridine-4-ium ylides by the
tandem reaction of methyl propiolate and DMAD with easily
accessible 10-cyanotetrahydrobenzo[b][1,6]naphthyridines. In-
vestigation of some chemical properties of these ylides is also
described.
(5) For selected papers on tandem reactions involving Michael addition see:
(a) Shigeta, Y.; Node, M.; Nishide, K.; Shiraki, H.; Obata, K. J. J. Am. Chem.
Soc. 2000, 9, 1927. (b) Bunce, R. A.; Herron, D. M.; Ackerman, M. L. J. Org.
Chem. 2000, 9, 2847. (c) Trost, B.; Yang, M.; Wuitschik, H. G. Org. Lett. 2005,
21, 4761. (d) Zu, L.; Wang, J.; Li, H.; Xie, H.; Jiang, W.; Wang, W. J. Am.
Chem. Soc. 2007, 5, 1036. (e) Jauch, J. J. Org. Chem. 2001, 2, 609. (g) Stelmakh,
A.; Stellfeld, T.; Kalesse, M. Org. Lett. 2006, 16, 3485.
(7) (a) Voskressensky, L. G.; Borisova, T. N.; Kulikova, L. N.; Varlamov,
A. V.; Catto, M.; Altomare, C.; Carotti, A. Eur. J. Org. Chem. 2004, 3128. (b)
Voskressensky, L. G.; Borisova, T. N.; Kostenev, I. S.; Kulikova, L. N.;
Varlamov, A. V. Tetrahedron Lett. 2006, 47, 999.
(6) For selected reviews on tandem reactions, see: (a) Tietze, L. F. Chem.
ReV. 1996, 96, 1, 115. (b) Winkler, J. D. Chem. ReV. 1996, 1, 167.
(8) Voskressensky, L. G.; Borisova, T. N.; Kostenev, I. S.; Vorobiev, I. V.;
Varlamov, A. V. Tetrahedron Lett. 2005, 46, 1975.
4596 J. Org. Chem. 2008, 73, 4596–4601
10.1021/jo8003698 CCC: $40.75 2008 American Chemical Society
Published on Web 05/28/2008

DeriVatiVes of Benzo[b]pyrrolo[2,1-f][1.6]naphthyridine
SCHEME 1. Transformations of Tetrahydrobenzonaph-
thyridines 1 and 2 under the Action of DMAD
SCHEME 2. Synthesis of the starting materials
FIGURE 1. X-ray crystal structure of the ylide (hydrate form) 7.
of the suitable monocrystal of the compound 7, obtained by
slow evaporation of its diluted methanolic solution (Figure 1).
The pyrroline fragment of the molecule is planar. The
N+(2)-C(12b) and N+(2)-C(3) (atom numbering according to
the X-ray structure in Figure 1) bond lengths (0.1480 and 0.1476
nm, respectively) are analogous to the N+-C in quaternary
ammonium salts. The CdO (0.1250 nm) bond is longer than
the average corresponding bond in OdC-CdC fragment
(0.1215 nm) denoting its participation in the negative charge
delocalization. We presume that the reaction starts with the
formation of the zwitterionic intermediate A, the anionic part
of which than cleaves one proton from the C1 methelene group,
thus producing ylide B, which can undergo two alternative
transformations, Stevens rearrangement10,11 (pathway a) or the
intramolecular SN reaction (pathway b), accompanying by the
elimination of the methoxide anion and pyrroline cycle forma-
tion (this process predominates under more forcing reaction
conditions). We presume that the configuration of the double
bond in the enamine fragment of B defines the reaction pathway:
the E-configuration favors the Stevens rearrangement, while
Z-configuration makes possible the nucleophilic attack and
formation of ylides 7-14 (Scheme 3).
Results and Discussion
Synthesis of the Ylides. The cyano-substituted tetrahy-
drobenzonaphthyridines (1-6), requisite for the present study,
were synthesized according to the protocol previously described
by condensation of isatines with γ-piperidones in the presence
of gaseous ammonia (Pfitzinger reaction), followed by the
dehydration reaction of the resulting 10-carbamoyl derivative8,9
(Scheme 2).
The reaction of derivatives 1-6 with methyl propiolate or
DMAD (1.2 molar excess) in boiling methanol for 2 h led to
the formation of intensively colored (usually red or brown)
powders, which were filtered off, washed with ethyl acetate,
and dried on air. Our attempts to recrystallize them failed, due
to the very low solubility of these compounds in common
organic solvents (except for DMSO or DMF). We were also
unable to elucidate their structures, based on common spectral
(1H, 13C NMR, mass spectra, IR) and microanalysis data. One
structure was assigned unambiguously by the X-ray analysis
The elemental analysis of compounds 7-14 (see Supporting
Information) shows that they did not form hydrates under the
usual reaction conditions; the formation of a crystalline hydrate
in the case of the ylide 7 is most likely attributed to the use of
water-containing methanol for recrystallization. We failed to
isolate ylide 9 in its pure form; under the reaction/separation
conditions it underwent the rearrangement to give 1-hydroxy
derivative 9a, which was isolated in 63% yield. However, the
formation of the ylide 9 was demonstrated by means of the NMR
analysis of the reaction mixture. Later on we managed to obtain
a monocrystal of water-free ylide 8, which was analyzed by
the X-ray diffraction method.
1
In the H NMR spectra of compounds 7-14, the protons of
CH2-5 and CH2-6 (see Scheme 3 for numbering) resonate in
(10) For selected papers on Stevens rearrangement, see: (a) Brewster, J. H.;
Kline, M. M. J. Am. Chem. Soc. 1953, 74, 5179. (b) Jenney, E. F.; Druey, J.
Angew. Chem., Int. Ed. 1962, 1, 155. (c) Blid, J.; Somfai, P. Tetrahedron Lett.
2003, 44, 3159.
(9) Gatto, F.; del-Giudice, M. R.; Mustazza, C. J. Heterocycl. Chem. 1996,
33, 1807.
(11) For a recent review on Stevens rearrangement, see: Vanecko, J. A.; Wan
H.; West, F. G. Tetrahedron 2006, 62, 1043.
J. Org. Chem. Vol. 73, No. 12, 2008 4597

Voskressensky et al.
SCHEME 3. Proposed Mechanism for the Formation of Ylides 7-14
the field of 3-4.5 ppm, one of the CH-5 protons being observed
as a dd signal around δ 4-4.5 ppm. 13C NMR spectra of ylides
7-14 showed the signal of C-1 carbon atom around 170 ppm,
some 20 ppm lower, than the usual signals of the carbonyl
carbons, once again denoting the participation of the unsaturated
ketone in the negative charge delocalization. The signal of the
ylidic carbon (C-12b) was registered at around 100 ppm, and
this value is analogous to those reported for the quinolizinium
SCHEME 4. Synthesis of 10-Methylbenzonaphthyridine 15
and Its Reaction with Methyl Propiolate
12
ylides.
We presumed that the presence of a strong electron-
withdrawing group in position 10 of the starting tetrahydroben-
zonaphthyridines is a must for this tetracyclic ylides formation.
In order to confirm or disprove this presumption, we synthesized
10-methyl13 substituted congener 15 and examined its reaction
with DMAD and methyl propiolate under similar reaction
conditions. Compound 15 was inert toward DMAD (only small
amounts of tarring products were formed after 12 h of refluxing
in dry methanol) but reacted with methyl propiolate, producing
2-vinylquinoline 16 in 12% yield (Scheme 4).
The formation of 2-vinyl quinoline derivative 16 may be
explained by the alternative cleavage of the most acidic proton
(C-4 methylene group) in the intermediate D by the in situ
formed methoxide anion, provoking a Hoffman-like elimination
reaction that led to the tetrahydropyridine ring cleavage (Scheme
5).
It was demonstrated that carbonyl-stabilized ammonium
ylides, depending on the reaction conditions, undergo either C-
or O-acylation.15 We studied the acetylation reaction of the
ylides 7-14 under the action of acetic anhydride. In all cases
the O-acetylation took place, accompanied by the elimination
of the N-Alk radical and subsequent aromatization of the
pyrroline fragment, yielding 1-acetoxypyrrolo[2,1-f]naphthy-
ridines 17-24 (Scheme 6). The structure of this new hetero-
cyclic system was confirmed by the X-ray analysis of the
compound 18, obtained by recrystallization from hexanes-ethyl
acetate mixture.
The reactivity of heterocyclic ammonium ylides has not been
exhaustively studied,14 basically due to the absence of prepara-
tive protocols for their synthesis. In this regard we were
interested in examining some reactions of ylides 7-14.
(14) For selected papers on heterocyclic ammonium ylides reactivity, see:
(a) Aggarwal, V. K.; Fang, G. Y.; Jonathan, P.; Charmant, H.; Graham, M. Org.
Lett. 2003, 5, 1757. (b) Audrey, A.; Larmanjat, B.; Marrot, J.; Couty, F.; David,
O. Chem. Commun. 2007, 2500. (c) Robiette, R.; Conza, M.; Aggarwal, V. K.
Org. Biomol. Chem. 2006, 4, 621.
(12) Kostik, E. I.; Abiko, A.; Oku, A. J. Org. Chem. 2001, 66, 1638.
(15) Chopard, P. A.; Searle, R. J. D.; Devitt, F. H. J. Org. Chem. 1965, 30,
1015.
(13) Oka, H.; Iida, M.; Sato, J.; Hondd, M. U.S. Patent 6.294.547B.1., 2001.
4598 J. Org. Chem. Vol. 73, No. 12, 2008

DeriVatiVes of Benzo[b]pyrrolo[2,1-f][1.6]naphthyridine
SCHEME 5. Mechanism of 2-Vinylquinoline 16 Formation.
to our tetracyclic ammonium ylides could provoke the C12b-N
bond cleavage, leading to formation of the nine-membered ring
(Scheme 9).
Having this idea in mind, we studied the reaction of ylides
7, 8, and 12 with freshly distilled benzaldehyde. In both cases
the reactions required heating and took around 6 h to finish.
The only products isolated were the corresponding 2-vinyl-3-
pyrrolylquinolines 29-31. We presume that compounds 7, 8,
and 12 reacted in their alcoholate form F, accepting a proton
from a molecule of benzoic acid (which resulted from the
oxidation of benzaldehyde), thus forming quarternary am-
monium salt G. The latter underwent Hoffman elimination under
the action of benzoate anion, yielding 2-vinyl quinolines 29-31.
The control reaction of the compounds 7, 8, and 12 with benzoic
acid led to the formation of 29-31 as well.
Inspection of the crystal packing of the compound 29 (suitable
monocrystal was obtained by recrystallization from ethyl acetate)
revealed that it consists of two crystallographically independent
types of molecules, differing mainly by the bonds lengths in
the pyrrole fragment. 3-Hydroxypyrrole moiety exists in its oxy-
form, being stabilized by hydrogen [OH · · ·N(quinoline)] bonding.
The planes of the quinoline and pyrrole rings are almost
perpendicular.
SCHEME 6. Acetylation of Compounds 7-14
We decided to investigate the reactivity of the ammonium
ylides under more forcing (classic Hoffman elimination reaction)
conditions; as expected under the action of a strong base, ylide
8 underwent six-membered ring opening, providing the corre-
sponding 2-vinyl quinoline 30 in good yields. (Scheme 10)
In conclusion, a variety of stable benzo[b]pyrrolo[2,1-f][1,6]
naphthyridine-4-ium ylides, representatives of a new heterocy-
clic system, were synthesized in good to high yields by the
reaction of acetylenic esters with easy obtainable tetrahydroben-
zonaphthyridines. The plausible mechanism of this one-pot
reaction includes the tandem Michael addition-Stevens
rearrangement-intramolecular SN reactions sequence. The
reactivity of the resulting ylides is mainly characterized by two
types of transformations: (1) cleavage of the alkyl radical from
the ylide nitrogen atom with concurrent addition of an electro-
phile to the oxygen atom, and (2) Hoffmann elimination
reaction, leading to the formation of 2-vinyl quinolines with
simultaneous aromatization of the pyrrolene moiety.
Experimental Section
The quinoline and pyrrole fragments of the tetracycle 18 are
planar, the torsion angle between these planes having the value
of 27°.
The starting 10-cyanobenzonaphthyridines 1-6 were synthesized
according to the protocol previously described.
8,18
General Procedure for Synthesis of Ylides 7-14. To the
solution of the corresponding 10-cyanobenzonaphthyridine 1-6
(2.24 mmol) in 40 mL of methanol was added 0.48 g (3.36 mmol)
of DMAD or 0.28 g (3.36 mmol) of methyl propiolate in one
portion, and the reaction mixture was refluxed for 2-3 h (TLC
monitoring, ethyl acetate). After the completion of the reaction,
the precipitate formed was collected by filtration and dried in air .
10-Methyl-2-isopropyl-1,2,3,4-tetrahydrobenzo[b][1.6]naph-
thyridine (15). The mixture of N-isopropylpiperidon-4 (5.00 g,
35.46 mmol) and 2-aminoacetophenone (5.27 g, 39.01 mmol) in
100 mL of absolute ethanol was stirred for 5 h at 70 °C, while
bubbling dry HCl gas through the reaction mixture. After the
completion of the reaction (TLC monitoring, ethyl acetate), the
reaction mixture was cooled, and the precipitate formed was
collected by filtration and dissolved in 100 mL of 20% NaOH .
The resulting solution was extracted with dichloromethane (3 ×
The acetylation of N-iPr ylides 9, 13, and 14 was accompanied
by the migration of the isopropyl radical to the R-position of
the pyrrole ring, presumably through the formation of the
quaternary salt E (Scheme 7).
The reactions of the ylides 7 and 8 with acid chlorides
proceeded analogously, providing the tetracyclic derivatives
25-28 (Scheme 8).
It was reported that ammonium ylides generated in situ
undergo an aldol-type reaction with aromatic aldehydes afford-
ing highly substituted amino acid frameworks in a convergent,
three-component reaction.16 A more recent paper describes the
epoxidation reaction of aryl-stabilized ammonium ylides under
the action of aromatic aldehydes.17 Applying these protocols
(16) Wang, Y.; Chen, Z.; Mi, A.; Hu, W. Chem. Commun. 2004, 2486.
(17) Papageorgiou, C. D.; Cubillo de Dios, M. A.; Ley, S. V.; Gaunt, M. J.
Angew. Chem., Int. Ed. 2004, 35, 4641.
(18) Voskressensky, L. G.; Borisova, T. N.; Listratova, A. V.; Vorobiev,
I. V.; Alexandrov, G. G.; Varlamov, A. V. J. Heterocycl. Chem. 2005, 42, 1207.
J. Org. Chem. Vol. 73, No. 12, 2008 4599

Voskressensky et al.
SCHEME 7. Acetylation of Compounds 9, 13, and 14 Accompanied by Migration of the iPr Radical
SCHEME 8. Reaction of Compounds 7 and 8 with Acid
Chlorides
J ) 12.7), 5.57 (dd, 1H, J ) 2.0, 10.6), 6.46 (dd, 1H, J ) 2.0,16.7),
6.94 (dd, 1H, J ) 10.6, 16.7), 7.45 (t,1H, J ) 7.4), 7.56(d, 1H, J
) 12.7), 7.64 (t, 1H, J ) 7.4), 7.92 (d, 1H, J ) 8.4), 8.03 (d, 1H,
J ) 8.4). 13C NMR (100 MHz, CDCl3): δ 14.5, 21.4 (2 × C), 45.0,
48.8, 50.5, 85.9, 122.6, 123.7, 123.8, 126.4, 127.2, 129.5, 130.2,
133.4, 144.5, 147.0, 147.1,155.1, 169.9. ESI MS: 325 (M+1) Anal.
Calcd for C20H24N2O2: C 74.07; H 7.41; N 8.64. Found: C 74.31;
H 7.59; N 8.82.
General Procedure for Acetylation of Compounds (7-14).
To the solution of a compound (7-14) (0.6 mmol) in 20 mL of
dichloromethane was added 0.07 g (0.66 mmol) of freshly distilled
acetic anhydride in one portion, and the reaction mixture was stirred
for 24 h at room temperature. The reaction mixture was subse-
quently treated with 20 mL of 10% Na2CO3 and 20 mL of water.
The organic layer was dried over MgSO4, the solvent was removed,
and the resulted yellowish oil was crystallized from diethyl ether
to give compounds 17-24.
10-Bromo-12-cyano-1,5,6,12b-tetrahydrobenzo[b]pyrrolo[2,1-
f]-1,6-naphthyridine-1-yl Acetate (20). Yellow solid 0.18 g (yield
78%), mp 186-188 °C. 1H NMR (400 MHz, CDCl3): 2.44(s, 3H),
3.40(t, 2H, J ) 5.9), 4.23(t, 2H, J ) 5.9), 6.38(d, 1H, J ) 2.6),
6.86(d, 1H, J ) 2.6), 7.80(d, 1H, J ) 8.5), 7.90(d, 1H, J ) 8.5),
8.37(s, 1H). 13C NMR (100 MHz, CDCl3): δ 21.6, 34.7, 44.0, 45.8,
104.1, 107.9, 113.8, 115.5, 122.6, 123.0, 125.7, 127.0, 130.7,133.2,
138.7, 143.1, 155.5, 168.4. EI MS m/z, (I %) 382(M+,1); 339(41);
286(7); 260(18); 204(8); 177(10), 151(7), 100(6), 75(7), 53(8),
43(100). Anal. Calcd for C18H12BrN3O2: C 56.54; H 3.14; N 10.99.
Found: C 56.37; H 3.37; N 10.83.
General Procedure for Reactions of Ylides 7 and 8 with
Cyclopropanecarbonyl Chloride or MsCl. To the solution of the
corresponding ylide (0.6 mmol) and 0.07 g (0.66 mmol) of NEt3
in 30 mL of dichloromethane was added 0.07 g (0.66 mmol) of
cyclopropanecarbonyl chloride or 0.08 g (0.66 mmol) of mesyl
chloride in one portion, and the reaction mixture was stirred at room
temperature for 12-18 h (TLC monitoring, ethyl acetate). The
reaction mixture was subsequently treated with 20 mL of 10% citric
acid, 20 mL of 10% Na2CO3, and 20 mL of water. The organic
layer was dried over Na2SO4 and evaporated to dryness. The
resulting viscous oil was triturated with diethyl ether to give
crystalline product, which was recrystallized from ethyl acetate/
hexane mixture.
100 mL). The organic extract was dried over MgSO4 followed by
the evaporation of the solvent under reduced pressure to give a
crystalline residue, which was recrystallized from ethyl acetate/
hexane mixture to yield 3.76 g (50%) of 15 as white solid, mp
100-102 °C. 1H NMR (400 MHz, CDCl3): 1.21 (d, 6H, J ) 6.5);
2.54 (s, 3H); 2.91 (T, 2H, J ) 5.7); 3.07 (spt, 1H, J ) 6.5); 3.22
(t, 2H, J ) 5.7); 3.92 (s, 2H); 7.49 (t, 1H, J ) 8.1); 7.61 (t, 1H, J
) 8.1); 7.97 (dd, 2H, J ) 4.0, 8.7). 13C NMR (100 MHz, DMSO):
δ 13.0, 18.3 (2 × C), 34.5, 45.1, 49.5, 53.9, 124.1, 125.8, 126.6,
127.6, 128.6, 129.0, 139.8, 146.2, 156.5 ESI MS: 241(M+ + 1).
Anal. Calcd for C16H20N2: C 80.00; H 8.33; N 11.67. Found: C
79.88; H 8.57; N 11.50.
12-Cyano-4-methyl-1-oxo-1,5,6,12b-tetrahydrobenzo[b]-
pyrrolo[2,1-f]-1,6-naphthyridine-4-ium Ylide (7). Orange solid
1
0.36 g (yield 27%). H NMR (400 MHz, DMSO): 3.32 (s, 3H),
3.71 (m, 2H), 4.32 (dd,2H, J ) 4.9,10.7), 6.68 (bs, 1H), 7.60 (m,
2H), 7.74(bs,1H), 7.88 (t, 2H, J ) 6.8). 13C NMR (100 MHz,
DMSO): δ 28.2, 49.9, 58.2, 99.5, 110.3, 116.8, 122.6, 126.3, 126.6,
126.8, 128.3, 128.7, 130.9, 141.9, 146.8, 150.0, 168.0. EI MS m/z,
(I %) 275(M+, 82); 260(40); 246(37); 232 (36); 222(39); 205(37);
191(21); 164(18); 152(21); 138(28); 126(55); 102(15); 84(30);
76(18); 57(30); 42(100). Anal. Calcd for C17H13N3O: C 74.18; H
4.73; N 15.27. Found: C 74.39; H 4.67; N 15.40.
(E)-Methyl-3-(isopropyl((4-methyl-2-vinylquinolin-3-yl)ami-
no)acrylate (16). The mixture of 15 (0.50 g, 2.36 mmol) and methyl
propiolate (0.28 g, 2.83 mmol) in 30 mL of absolute methanol was
refluxed for 12 h. The solvent was evaporated under reduced
pressure, the resulted yellow oil was purified by column chroma-
tography (column size 2 × 20 cm, eluent ethyl acetate/hexane 1:10
mixture) to give 80 mg (12%) of 16 as colorless prisms with mp
118-120 °C. 1H NMR (400 MHz, CDCl3): 1.05 (d, 6H, J ) 6.7),
2.60 (s, 3H), 3.06(m,1H), 3.70 (s, 3H), 4.41 (s, 2H), 4.97 (d, 1H,
Methyl 12-Cyano-1-[(cyclopropylcarbonyl)oxy]-5,6-dihydro-
benzo[b]pyrrolo[2,1-f][1,6]naphthyridine-3-carboxylate (26). Yel-
low solid (yield 93%), mp 180-182 °C. 1H NMR (400 MHz,
CDCl3): 1.05(m,2H), 1.18(m,2H), 2.03(m,1H), 3.41(t, 2H, J ) 6.2),
3.87 (s, 3H), 4.85(t, 2H, J ) 6.2), 7.08 (s, 1H), 7.72(t, 1H, J )
4600 J. Org. Chem. Vol. 73, No. 12, 2008

DeriVatiVes of Benzo[b]pyrrolo[2,1-f][1.6]naphthyridine
SCHEME 9. Hoffman-like Cleavage of the Tetrahydropyridine Ring in Compounds 7, 8, and 12 under the Action of Benzoic
Acid
SCHEME 10. Hoffman-like Cleavage of 8
mmol) in 20 mL of dichloromethanewas added 0.08 g (0.66 mmol)
of benzoic acid in one portion, and the reaction mixture was stirred
for 24 h at room temperature. The reaction mixture was subse-
quently treated with 20 mL of 10% Na2CO3 and 20 mL of water.
The organic layer was dried over MgSO4, and the solvent was
removed to give crystalline compounds 29-31.
Methyl 5-(4-Cyano-2-vinylquinolin-3-yl)-4-hydroxy-1-methyl-
1H-pyrrole-2-carboxylate (30). Yellow solid (yield 35%), mp
200-202 °C. H NMR (400 MHz, CDCl3): 3.58(s, 3H), 3.84(s,
7.3), 7.81(t, 1H, J ) 7.3), 8.10(d, 1H, J ) 8.1), 8.28(d, 1H, J )
8.1). 13C NMR (100 MHz, CDCl3): δ 9.8, 13.3, 33.8, 41.2, 51.7,
110.7, 112.5, 115.0, 119.9, 121.7, 123.9, 125.1, 126.3, 128.8, 129.1,
130.9, 137.3, 144.7, 155.6, 160.9, 172.2. ESI MS: 388(M+ + 1).
Anal. Calcd for C22H17N3O4: C 68.21; H 4.39; N 10.85. Found: C
68.00; H 4.49; N 10.92.
Methyl 12-Cyano-1-[(methylsulfonyl)oxy]-5,6-dihydrobenzo-
[b]pyrrolo[2,1-f][1,6]naphthyridine-3-carboxylate (28). Pale-red
solid (yield 73%), mp 222-224 °C. 1H NMR (400 MHz, CDCl3):
3.33(s,3H), 3.45(t, 2H, J ) 6.2), 3.89(s, 1H), 4.85(t, 2H, J ) 6.2),
7.12(s, 1H), 7.73(t, 1H, J ) 7.6), 7.82(t, 1H, J ) 7.6), 8.11(d, 1H,
J ) 8.3), 8.27(d, 1H, J ) 8.3). 13C NMR (100 MHz, DMSO): δ
33.8, 37.8, 41.6, 51.9, 110.6, 112.8, 115.1, 121.4, 121.9, 123.0,
125.3, 126.12, 129.0, 129.2, 131.3, 133.4, 145.2, 155.3, 160.6. EI-
MS: m/z (%): 397 (M+, 10); 318(100); 230(12); 206(16); 191(9);
178(6); 152(7), 102(5), 79(38), 59(10), 53(22). Anal. Calcd for
C19H15N3O5S: C 57.42; H 3.78; N 10.58. Found: C 57.25; H 3.60;
N 10.76.
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3H), 5.61(d, 1H, J ) 10.8), 6.57(d, 1H, J ) 16.1), 6.65-6.71(m,1H),
6.69(s, 1H), 7.09(bs,1H(-OH)), 7.65(t, 1H, J ) 7.3), 7.84(t, 1H, J
) 7.3), 8.06(d, 1H, J ) 8.1), 8.16(d, 1H, J ) 8.1). 13C NMR (100
MHz, CDCl3): δ 33.9, 51.6, 106.2, 114.4, 118.3, 121.5, 122.2,
124.5, 124.7, 125.2, 126.3, 129.2(2 × C), 132.2, 132.6, 142.1, 147.0,
155.5, 161.5. ESI MS: 334(M++1). Anal. Calcd for C19H15N3O3:
C 68.46; H 4.50; N 12.61. Found: C 68.25; H 4.67; N 12.39.
Acknowledgment. We thank the Russian Foundation for
Basic Research for its financial support (Grant no. 07-03-12029-
ofi).
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Supporting Information Available: H and 13C NMR, EI
or ESI mass spectra, and elemental analysis data for compounds
1-31; CIF files for all X-ray analyses mentioned. This material
is available free of charge via the Internet at http://pubs.acs.org.
General Procedure for Reaction of Ylides 7, 8, and 12
with Benzoic Acid. To the solution of the ylide (7, 8, 12) (0.6
JO8003698
J. Org. Chem. Vol. 73, No. 12, 2008 4601