Vinylation of nitro-substituted indoles, quinolinones, and anilides with grignard reagents

Article abstract of DOI:10.1002/chem.200901322

The reaction of vinyl Grignard reagents with omethoxynitroarenes containing an electron-releasing substituent para to the nitro group proceeds through a pathway that is different from the initially expected Bartoli indole synthesis. Thus, instead of givin

Full text of DOI:10.1002/chem.200901322

DOI: 10.1002/chem.200901322
Vinylation of Nitro-Substituted Indoles, Quinolinones, and Anilides with
Grignard Reagents
Riccardo Egris, Mercedes Villacampa, and J. Carlos Menꢀndez*[a]
Abstract: The reaction of vinyl
Grignard reagents with o-methoxyni-
troarenes containing an electron-releas-
ing substituent para to the nitro group
proceeds through a pathway that is dif-
ferent from the initially expected Bar-
toli indole synthesis. Thus, instead of
giving fused indole derivatives, these
reactions provide a very mild and effi-
cient new procedure for the synthesis
of synthetically relevant aromatic sys-
tems containing an o-nitrovinyl moiety,
such as 5-nitro-4-vinylindoles, 6-nitro-
Keywords: aromatic compounds ·
7-vinylindoles,
6-nitro-5-vinyl-
À
C C coupling · Grignard reaction ·
2(1H)quinolinones, and 4-nitro-3-vinyl-
anilines.
heterocycles · vinyl compounds
Introduction
The indole nucleus is one of the most important heterocyclic
systems. Indole derivatives are widespread in nature[1] and
are also present in a large number of bioactive compounds.
Indeed, indole derivatives have been included in the “privi-
leged scaffolds” cathegory[2] because they comply with the
definition proposed by Evans in that they constitute “a mo-
lecular framework able to provide ligands for diverse recep-
tors”.[3] For this reason, the preparation of substituted and
functionalized indoles has attracted the attention of synthet-
ic chemists for over a century.[4] In 1989, the Bartoli group
described that the reaction between nitroarenes bearing one
substituent ortho to the nitro group and vinyl Grignard re-
agents affords 7-substituted indole derivatives,[5] a reaction
that has subsequently become known as the Bartoli indole
synthesis[6] and can be considered as one of the most inter-
esting recent methods for the preparation of indoles.[7] Its
mechanism is complex and not completely understood, but
it is assumed to involve two consecutive additions of a vinyl
Grignard reagent to the oxygen atom in the N=O bond of a
nitro group, initially, and of a nitroso group at a later stage.
As shown in Scheme 1, we describe here that the conjuga-
tion of the nitro group with electron-releasing substituents
Scheme 1. Comparison of the Bartoli indole synthesis with the reactions
described in this article.
(D) hampers this reaction and deviates its course towards
aromatic vinylation through a mechanism involving a conju-
gate addition to an o-methoxynitroarene system followed by
elimination. This very simple route to 2-vinylnitroarene sys-
tems is of relevance in the preparation of complex fused
heterocyclic systems, in view of the many synthetic possibili-
ties afforded by the two adjacent functional groups. Previous
studies on the synthesis of 2-vinylnitroarenes are scarce in
the literature and have focused on benzene derivatives and
involve palladium-catalyzed cross-coupling reactions of 2-
halonitroarenes, such as the Heck,[8] Stille,[9] and Suzuki[10]
[a] R. Egris, Prof. M. Villacampa, Prof. J. C. Menꢀndez
Departmento de Quꢁmica Orgꢂnica y Farmacꢀutica
Universidad Complutense, Facultad de Farmacia
28040 Madrid (Spain)
Fax : (+34)91-3941822
E-mail: josecm@farm.ucm.es
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901322.
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Chem. Eur. J. 2009, 15, 10930 – 10939

FULL PAPER
reactions. Since these methods normally require forcing con-
ditions, such as prolonged reflux (up to 70 h) and also in-
volve expensive ligands and palladium catalysts, the devel-
opment of milder and simpler alternatives is of considerable
interest.
Our studies mainly involved indole vinylation because of
the intrinsic value of indoles and also because, due to the
above-mentioned challenges posed by the preparation of 2-
nitrovinylarene systems, indole derivatives that contain this
structural feature are almost unknown in the literature, al-
though they would be of great synthetic value. To mention
one example of the potential applications of this structural
feature, the coupling of a procedure for o-nitrovinylindole
generation with the well-known one-step transformation of
2-nitrovinylarenes into indoles[11] would lead to a two-step
Scheme 2. Synthesis of indoles 3 and 4 as starting materials.
synthesis of substituted derivatives of the pyrrolo
e]indole and pyrrolo[2,3-f]quinoline ring systems, both of
which are biologically very relevant. Thus, the pyrrolo[3,2-
ACHTUNGTNER[NUNG 3,2-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Table 1. Yields obtained in the preparation of indole derivatives 1–4.
e]indole system is the main structural fragment of a family
of minor groove-alkylating antitumor agents[12] that include
the natural product CC-1065 and synthetic, less toxic ana-
logues such as bizelesin.[13] On the other hand, many simple
Bartoli reaction[a]
Methylation[b]
Compd. R1
R2
t
Yield
[%]
Compd. R1
R2
Yield
[%]
[h]
1a
1b
1c
2a
2b
2c
2d
H
CH3
H
H
CH3
H
H
H
CH3
H
H
2
3
3
1
2
2
3
60
47
60
51
45
52
51
3a
3b
3c
4a
4b
4c
4d
H
H
90
96
96
96
92
derivatives of the pyrroloACTHNURTGNEU[GN 2,3-f]quinoline system have been
CH3
H
H
H
CH3
H
identified as potent antitumor agents.[14]
CH3
H
H
H
CH3
C6H5
CH3
C6H5
100
93
Results and Discussion
H
[a] Reaction conditions: Grignard reagent, THF, À788C, 2–3 h. [b] Re-
action conditions: NaH, ICH3, THF, 08C, 1 h; then RT, 4 h.
We began our work by starting from derivatives of 1-
methyl-4,7-dimethoxy-5-nitroindole (3) and 1-methyl-4,7-di-
methoxy-6-nitroindole (4), which were prepared according
to Scheme 2 and Table 1. Application of the Bartoli indole
synthesis to 1,4-dimethoxy-2,5-dinitrobenzene[15] gave fair
yields of indoles 1, which were later methylated to com-
pounds 3. A similar sequence starting from 2,5-dimethoxy-
1,3-dinitrobenzene[16] afforded 4-methoxy-6-nitroindoles 2,
which were methylated to give compounds 4. The prepara-
tion of compounds 1 and 2, to our knowledge, represents
the first example of a Bartoli reaction on dinitrobenzene
substrates and hence the first use of the Bartoli reaction to
install a nitrogen function at the indole C-5 and C-6 posi-
tions. Probably because of the activation provided by the ad-
ditional nitro group, the reactions had to be carried out at
À788C, which is a lower temperature than that normally
used for the Bartoli indole synthesis.
The results obtained in the reaction of compounds 3 with
a variety of vinylmagnesium bromides are summarized in
Scheme 3 and Table 2. In all cases studied, compounds aris-
ing from a Bartoli reaction were not observed and the only
products formed in the reaction were compounds 5, arising
from vinylation of the highly hindered indole C-4 position,
presumably through an addition–elimination mechanism. It
is noteworthy that compounds 5 were obtained in yields of
90% or higher, with the only exception of 5d (70% yield).
The latter result was probably due to the steric hindrance
associated with the presence of a substituent a to the nucle-
ophilic center (R3 =CH3). When the same conditions were
applied to compound 1a, not bearing a N-methyl substitu-
ent, the starting material was essentially recovered un-
changed, showing that the presence of a negative charge
generated by deprotonation of the indole nitrogen does not
allow the subsequent approach of the Grignard reagent.
We next examined the reaction of vinyl Grignard reagents
with 6-nitroindole derivatives 4. Again, the aromatic vinyla-
tion proceeded smoothly and afforded good to excellent
yields of compounds 6, vinylated at the hindered indole C-7
position (Scheme 4 and Table 3). These results, taken in the
aggregate with those summarized in Scheme 3 and Table 2,
prove that the combination of the Bartoli indole synthesis
with our vinylation protocol allows the very concise prepara-
Abstract in Spanish: La reacciꢀn entre vinilmagnesianos y o-
metoxinitroarenos con un grupo donador electrꢀnico en posi-
ciꢀn para respecto al grupo nitro no tiene lugar a travꢁs de
una sꢂntesis de indoles de Bartoli, como cabrꢂa esperar en
principio. Se observa, en cambio, una reacciꢀn de vinilaciꢀn
aromꢃtica en condiciones muy suaves que conduce a sistemas
aromꢃticos con un fragmento de o-nitrovinilareno, incluyen-
do derivados de 5-nitro-4-vinilindol, 6-nitro-7-vinilindol, 6-
nitro-5-vinil-2ACHTUNGTRENNUNG(1H)quinolinona y 4-nitro-3-vinilanilina.
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J. C. Menꢀndez et al.
Table 3. Yields obtained in the preparation of compounds 6.[a]
Compd.
R1
R2
R3
R4
R5
t [h]
Yield [%]
6a
6b
6c
6d
6e
6 f
6g
6h
6i
6j
6k
6l
6m
6n
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
H
H
H
CH3
H
H
H
H
CH3
C6H5
H
H
H
CH3
H
H
1
1
1
5
1
2
2
2
2
1
3
2
3
5
91
99
94
98
75
95
98
72
71
96
97
85
81
98
CH3
CH3
H
H
H
CH3
CH3
H
H
CH3
H
H
CH3
CH3
CH3
CH3
H
H
H
H
C6H5
H
CH3
CH3
CH3
CH3
H
H
CH3
H
H
H
CH3
H
CH3
CH3
H
[a] Reaction conditions: Grignard reagent, THF, À508C, 1–5 h.
Scheme 3. Vinylation of the C-4 position of indoles 3 to give 5.
Table 2. Yields obtained in the preparation of compounds 5.[a]
Compd.
R1
R2
R3
R4
R5
t [h]
Yield [%]
5a
5b
5c
5d
5e
5 f
5g
5h
5i
H
H
H
CH3
H
H
H
H
H
CH3
CH3
CH3
H
H
H
H
H
H
CH3
H
H
H
H
H
H
H
H
CH3
H
H
H
CH3
H
H
CH3
H
5
5
4
5
3
3
3
3
5
3
4
4
95
88
96
70
90
90
94
95
91
90
91
90
CH3
CH3
H
H
H
H
CH3
CH3
H
CH3
CH3
C6H5
C6H5
CH3
CH3
CH3
CH3
H
Figure 1. Conjugation of the nitro group with an electron-releasing
moiety in the starting materials used for our vinylation reactions.
5j
5k
5l
H
H
H
H
CH3
H
[a] Reaction conditions: Grignard reagent, THF, À508C, 1–5 h.
carry out synthetically useful vinylations on other aromatic
systems containing electron-releasing substituents conjugat-
ed with the nitro group. To verify this hypothesis, we briefly
examined the reaction of vinylmagnesium bromides with
some aromatic compounds containing a 1-nitro-2-methoxy-
4-acylaminobenzene fragment. To this end, we selected as
starting materials carbostyril derivative 7, due to the biologi-
cal significance of the 2(1H)quinolinone (carbostyril) unit,[18]
and also two simple anilides 8 (Figure 1).
Scheme 4. Vinylation of the C-7 position of indoles 4 to give 6.
Compound 7 was initially prepared by nitration of the
known[19] carbostyril derivative 9, but this procedure posed
some problems due to difficulties in scaling up the prepara-
tion of the starting material. As an alternative, we devel-
oped another route in which the N-demethyl analogue of 9
(compound 10), readily available on a multigram scale,[20]
was regioselectively nitrated at C-6 to give 11 and then N-
methylated under phase-transfer conditions. The synthesis
of 7, together with the results obtained in its reaction with
vinyl Grignard reagents, are summarized in Scheme 5.
Again, the use of our standard conditions (THF, À508C) led
to the isolation of 5-vinyl-2(1H)quinolinones 12 in good to
excellent yields,[21] although in this case the reactions involv-
ing the more hindered a-substituted Grignard reagents
failed to give vinylation products.
tion of indole derivatives functionalized at the hindered C-4
or C-7 positions. This is a significant achievement in that, al-
though there are many examples of efficient syntheses of in-
doles substituted at the 3- and 5-positions, the functionaliza-
tion of their 4- and 7-positions has been much less stud-
ied.[17]
The observed preference towards aromatic vinylation in
both indole systems can be attributed to the fact that direct
conjugation with the indole nitrogen renders the O=N bond
of the nitro group insufficiently electrophilic to be attacked
by the Grignard reagent, as shown in Figure 1. According to
this assumption, we postulated that it should be possible to
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Vinylation of Nitro-Substituted Indoles, Quinolinones, and Anilides
FULL PAPER
63–64% range, somewhat lower than in other cases owing
to some accompanying deacetylation of the starting materi-
al. The transformation of 8b into 13b is interesting in that it
shows that the second methoxy group, present in most of
our starting materials because it facilitated their prepara-
tion, is not a requisite for the vinylation process.
Conclusion
We have shown that vinyl Grignard reagents can react with
o-methoxynitroarenes through a pathway that is different
from the Bartoli indole synthesis, which has led to the dis-
covery of a very mild, concise, and efficient new procedure
for aromatic vinylation and its application to the synthesis
of aromatic systems containing an o-nitrovinyl moiety,
which are synthetically relevant and difficult to generate by
using conventional methodologies. These systems include 5-
nitro-4-vinylindoles, 6-nitro-7-vinylindoles, 6-nitro-5-vinyl-
2(1H)quinolinones, and 4-nitro-3-vinylanilines. This behav-
ior was hitherto unknown for the reaction of vinyl Grignard
reagents with o-methoxynitroarenes, although naphthyl
Grignards were known to give 2-nitro-1,1’-binaphthyls upon
treatment with 1-methoxy-2-nitronaphthalenes[22] and
phenyl Grignards gave mixtures of 4-phenyl-5-nitro-2-
(1H)quinolinones and 5-phenylamino-4-methoxy-2-(1H)qui-
nolinones by reaction with 4-methoxy-5-nitro-2-(1H)quino-
linones.[23] It must be remembered, however, that vinyl and
aryl Grignard reagents often show different reactivity
Scheme 5. Synthesis of compound 7 and studies on the vinylation of its
C-5 position by Grignard reagents.
Finally, two examples of structure 8 (compounds 8a
and b) were prepared from the corresponding anilides by
using standard nitration and N-methylation conditions and
treated with vinylmagnesium bromide, leading to com-
pounds 13, in which the expected vinylation was accompa-
nied by N-deacetylation (Scheme 6). The yields were in the
AHCTUNGTRENNUNG
patterns.[6,24]
Experimental Section
General experimental information: All reagents (Aldrich, Fluka, SDS,
Probus) and solvents (SDS) were of commercial quality and were used as
received. Reactions were monitored by TLC, on aluminum plates coated
with silica gel with fluorescent indicator (SDS CCM221254). Separations
by flash chromatography were performed on silica gel (SDS 60 ACC 40–
63 mm). Melting points were measured on a Reichert 723 hot stage micro-
scope, and are uncorrected. IR spectra were recorded on a Perkin–Elmer
Paragon 1000 FTIR spectrophotometer, with all compounds examined as
thin films on NaCl disks. NMR spectra were obtained on Bruker Avance
1
250 and 500 spectrometers operating at 250 or 500 MHz for H and 63 or
125 MHz for 13C (CAI de Resonancia Magnꢀtica Nuclear, Universidad
Complutense). Elemental analyses were determined by the CAI de Mi-
croanꢂlisis Elemental, Universidad Complutense, by using a Leco 932
CHNS combustion microanalyzer.
General procedure for the Bartoli reactions: Preparation of compounds
1 and 2: The suitable vinylmagnesium reagent (30 mmol, as a commer-
cially available solution in THF) was added dropwise to
a cooled
(À788C) solution of 2,5-dimethoxy-1,3-dinitrobenzene or 1,4-dimethoxy-
2,5-dinitrobenzene (10 mmol) in dry THF (150 mL), under an argon at-
mosphere. The reaction mixture was stirred at the same temperature for
1–3 h and was then poured onto a saturated aqueous NH4Cl solution
(75 mL), which was extracted with AcOEt (3ꢄ50 mL). The combined or-
ganic extracts were dried (anhydrous Na2SO4) and evaporated, and the
residue was purified by fast chromatography on silica gel, eluting with a
5:1 petroleum ether/ethyl acetate mixture.
4,7-Dimethoxy-5-nitroindole (1a): Yellow solid; yield: 1.340 g, 60%; m.p.
86–888C; IR (neat): n˜ =1523, 1339 (NO2), 1197 cmÀ1 (OCH3); 1H NMR
Scheme 6. Vinylation of anilides 8 by vinylmagnesium bromide.
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J. C. Menꢀndez et al.
(250 MHz, CDCl3): d=8.84 (s, 1H; NH); 7.30–7.27 (m, 1H; H2), 7.24 (s,
1H; H6), 6.83 (dd, 1H, J=3.2, 2.3 Hz; H3), 4.15 (s, 3H; OCH3), 3.93 ppm
(s, 3H; OCH3); 13C NMR (63 MHz, CDCl3): d=144.4 (C4), 141.3 (C7),
134.5 (C5), 130.4 (C7a), 125.1 (C2), 122.1 (C3a), 103.3 (C3), 98.6 (C6), 62.1
(OCH3), 55.9 ppm (OCH3); elemental analysis calcd (%) for C10H10N2O4:
C 54.05, H 4.54, N 12.61; found: C 54.35, H 4.32, N 12.39.
(11 mmol) was added and stirring was maintained for 4 h, allowing the
reaction to reach room temperature. The reaction mixture was poured on
ice (20 mL) and was extracted with ethyl acetate (3ꢄ30 mL). The com-
bined extracts were dried (anhydrous Na2SO4) and evaporated, affording
the methylindoles.
1-Methyl-4,7-dimethoxy-5-nitroindole (3a): Pale-brown solid; yield:
1.060 g, 90%; m.p. 102–1048C; IR (neat): n˜ =1519, 1324 (NO2), 1226
cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.23 (s, 1H; H6), 7.0 (d,
1H, J=3.1 Hz; H2), 6.70 (d, 1H, J=3.1 Hz; H3), 4.08 (s, 3H; OCH3),
4.07 (s, 3H; N-CH3), 3.96 ppm (s, 3H; OCH3); 13C NMR (63 MHz,
CDCl3): d=144.3 (C4), 143.2 (C7), 133.7 (C5), 131.3 (C2), 130.1 (C8), 124.1
2-Methyl-4,7-dimethoxy-5-nitroindole (1b): Yellow solid; yield: 1.114 g,
47%; m.p. 129–1318C; IR (neat): n˜ =3396 (NH), 1515, 1305 (NO2),
1223 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=8.70 (s, 1H; NH),
7.17 (s, 1H; H6), 6.47–6.46 (m, 1H; H3), 4.01 (s, 1H; OCH3), 3.93 (s, 3H;
OCH3), 2.46 ppm (s, 3H; CH3); 13C NMR (63 MHz, CDCl3): d=143.7
(C4), 140.7 (C7), 136.4 (C2), 134.0 (C5), 130.5 (C7a), 122.8 (C3a), 100.6 (C3),
97.9 (C6), 61.8 (OCH3), 55.8 (OCH3), 13.4 ppm (C2-CH3); elemental anal-
ysis calcd (%) for C11H12N2O4: C 55.93, H 5.08, N 11.86; found: C 56.06,
H 5.09, N 11.52.
À
(C9), 101.6 (C3), 98.5 (C6), 64.2 (OCH3), 55.9 (OCH3), 36.5 ppm (N
CH3); elemental analysis calcd (%) for C11H12N2O4: C 55.93, H 5.08, N
11.86; found: C 55.60, H 5.23, N 12.02.
1,2-Dimethyl-4,7-dimethoxy-5-nitroindole (3b): Pale-yellow solid; yield:
1.201 g, 96%; m.p. 128–1298C; IR (neat): n˜ =1524, 1319 (NO2), 1220
cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.19 (s, 1H; H6), 6.50 (d,
1H, J=0.9 Hz; H3), 4.06 (s, 3H; OCH3), 3.98 (s, 3H; OCH3), 3.97 (s, 3H;
3-Methyl-4,7-dimethoxy-5-nitroindole (1c): Yellow solid; yield: 1.417 g,
60%; m.p. 108–1108C; IR (neat): n˜ =3339 (NH), 1515, 1315 (NO2),
1223 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=8.43 (s, 1H; NH),
7.27 (s, 1H; H6), 7.00 (s, 1H; H2), 4.02 (s, 3H; OCH3), 4.01 (s, 3H;
OCH3), 2.51 ppm (s, 3H; CH3); 13C NMR (63 MHz, CDCl3): d=146.1
(C4), 141.6 (C7), 134.4 (C5), 131.2 (C7a), 123.2 (C2), 122.2 (C3a), 114.9 (C3),
98.7 (C6), 63.4 (OCH3), 57.4 (OCH3), 11.3 ppm (C3-CH3); elemental anal-
ysis calcd (%) for C11H12N2O4: C 55.93, H 5.08, N 11.86; found: C 56.29,
H 5.17, N 11.68.
N CH3), 2.42 ppm (d, 3H, J=0.9 Hz; C2-CH3); 13C NMR (63 MHz,
À
CDCl3): d=143.7 (C4), 142.7 (C7), 139.3 (C2), 133.4 (C5), 130.5 (C7a),
À
123.4 (C3a), 100.3 (C3), 98.3 (C6), 61.9 (OCH3), 56.2 (OCH3), 32.7 (N
CH3), 12.9 ppm (C2-CH3); elemental analysis calcd (%) for C12H14N2O4:
C 57.60, H 5.60, N 11.20; found: C 57.39, H 5.34, N 11.31.
1,3-Dimethyl-4,7-dimethoxy-5-nitroindole (3c): Pale-yellow solid; yield:
1.204 g, 96%; m.p. 64–668C; IR (neat): n˜ =1518, 1323 (NO2), 1216 cmÀ1
(OCH3); 1H NMR (250 MHz, CDCl3): d=7.21 (s, 1H; H6), 6.73 (s, 1H;
4,7-Dimethoxy-6-nitroindole (2a): Yellow solid; yield: 1.132 g, 51%; m.p.
138–1408C; IR (neat): n˜ =1519, 1315 (NO2), 1284 cmÀ1 (OCH3);
1H NMR (250 MHz, CDCl3): d=8.81 (s, 1H; NH), 7.39 (dd, 1H, J=2.9,
2.7 Hz; H2), 7.17 (s, 1H; H5), 6.74 (dd, 1H, J=2.9, 2.3 Hz; H3), 4.08 (s,
3H; OCH3), 4.01 ppm (s, 3H; OCH3); 13C NMR (63 MHz, CDCl3): d=
148.9 (C4), 137.8 (C7), 136.1 (C6), 130.5 (C7a), 128.1 (C2), 125.2 (C3a),
102.2 (C3), 96.5 (C5), 62.8 (OCH3), 56.3 ppm (OCH3); elemental analysis
calcd (%) for C10H10N2O4: C 54.05, H 4.50, N 12.61; found: C 54.46, H
4.73, N 12.32.
À
H2), 3.98 (s, 3H; OCH3), 3.97 (s, 3H; OCH3), 3.94 (s, 3H; N CH3),
2.45 ppm (d, 3H, J=0.9 Hz; C3-CH3); 13C NMR (63 MHz, CDCl3): d=
146.2 (C4), 143.2 (C7), 133.4 (C5), 130.8 (C7a), 129.9 (C2), 123.4 (C3a),
À
113.4 (C3), 98.7 (C6), 63.1 (OCH3), 55.8 (OCH3), 36.1 (N CH3), 11.2 ppm
(C3-CH3); elemental analysis calcd (%) for C12H14N2O4: C 57.60, H 5.60,
N 11.20; found: C 57.42, H 5.41, N 11.55.
1-Methyl-4,7-dimethoxy-6-nitroindole (4a): Pale-brown solid; yield:
1.133 g, 96%; m.p. 111–1138C; IR (neat): n˜ =1522, 1337 (NO2), 1213
cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.11 (d, 1H, J=3 Hz;
H2), 7.07 (s, 1H; H5), 6.57 (d, 1H, J=3 Hz; H3), 4.07 (s, 3H; OCH3), 3.99
2-Methyl-4,7-dimethoxy-6-nitroindole (2b): Yellow solid; yield: 1.062 g,
45%; m.p. 128–1308C; IR (neat): n˜ =3394 (NH), 1519, 1315 (NO2),
1284 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=8.92 (s, 1H; NH),
7.16 (s, 1H; H5), 6.38 (dd, 1H, J=2.3, 0.7 Hz; H3), 4.05 (s, 3H; OCH3),
3.95 (s, 3H; OCH3), 2.50 ppm (d, 3H, J=0.7 Hz; C2-CH3); 13C NMR
(63 MHz, CDCl3): d=147.5 (C4), 139.7 (C7), 136.9 (C2), 134.4 (C6), 129.7
(C7a), 125.9 (C3a), 99.7 (C3), 96.2 (C5), 62.2 (OCH3), 55.7 (OCH3),
13.8 ppm (C2-CH3); elemental analysis calcd (%) for C11H12N2O4: C
55.96, H 5.08, N 11.86; found: C 56.15, H 5.24, N 11.52.
(s, 3H; OCH3), 3.95 ppm (s, 3H; N CH3); 13C NMR (63 MHz, CDCl3):
À
d=148.6 (C4), 139. 3 (C7), 135.0 (C6), 134.2 (C2), 129.6 (C7a), 126.6 (C3a),
100.2 (C3), 96.4 (C5), 64.0 (OCH3), 56.2 (OCH3), 36.4 ppm (N-CH3); ele-
mental analysis calcd (%) for C11H12N2O4: C 55.93, H 5.08, N 11.86;
found: C 55.57, H 4.88, N 12.16.
1,2-Dimethyl-4,7-dimethoxy-6-nitroindole (4b): Pale-brown solid; yield:
1.152 g, 92%; m.p. 128–1308C; IR (neat): n˜ =1515, 1330 (NO2),
1209 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.14 (s, 1H; H5),
3-Methyl-4,7-dimethoxy-6-nitroindole (2c): Yellow solid; yield: 1.228 g,
52%; m.p. 147–1498C; IR (neat): n˜ =3340 (NH), 1515, 1312 (NO2),
1228 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=8.57 (s, 1H; NH),
7.11 (d, 1H, J=1.1 Hz; H2), 7.10 (s, 1H; H5), 4.04 (s, 3H; OCH3), 3.96 (s,
3H; OCH3), 2.46 ppm (d, 3H, J=1.1 Hz; C3-CH3); 13C NMR (63 MHz,
CDCl3): d=150.2 (C4), 137.2 (C7), 135.2 (C6), 130.7 (C7a), 125.6 (C2),
123.8 (C3a), 114.2 (C3), 95.5 (C5), 62.2 (OCH3), 55.7 (OCH3), 11.5 ppm
(C3-CH3); elemental analysis calcd (%) for C11H12N2O4: C 55.96, H 5.08,
N 11.86; found: C 55.85, H 5.05, N 11.67.
À
6.41 (d, 1H, J=0.8 Hz; H3), 4.00 (s, 6H; OCH3, N CH3), 3.97 (s, 3H;
OCH3), 2.45 ppm (d, 3H, J=0.8 Hz; C2-CH3); 13C NMR (63 MHz,
CDCl3): d=147.3 (C4), 141.9 (C2), 138.4 (C7), 135.4 (C6), 129.3 (C7a),
125.4 (C3a), 99.1 (C3), 96.2 (C5), 63.4 (OCH3), 55.8 (OCH3), 31.8 (N-CH3),
13.1 ppm (C2-CH3); elemental analysis calcd (%) for C12H14N2O4: C
57.59, H 5.64, N 11.19; found: C 57.81, H 5.79, N 10.85.
1,3-Dimethyl-4,7-dimethoxy-6-nitroindole (4c): Pale-yellow solid; yield:
1.251 g, 100%; m.p. 83–858C; IR (neat): n˜ =1515, 1336 (NO2), 1193 cmÀ1
(OCH3); 1H NMR (250 MHz, CDCl3): d=6.97 (s, 1H; H5), 6.79 (d, 1H,
4,7-Dimethoxy-6-nitro-3-phenylindole (2d): Pale-brown solid; yield:
1.520 g, 51%; m.p. 132–1348C; IR (neat): n˜ =3338 (NH), 1520, 1318
(NO2), 1220 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=9.97 (s, 1H;
NH), 7.65–7.62 (m, 2H; Ar-H), 7.48–7.33 (m, 4H; Ar-H, H2), 7.20 (s, 1H;
H5), 4.07 (s, 3H; OCH3), 3.83 ppm (s, 3H; OCH3); 13C NMR (63 MHz,
CDCl3): d=150.1 (C4), 138.2 (C7), 137.1 (C6), 135.6 (C1’), 133.8 (C2),
129.7 (C7a), 129.2, 128.0 (C2’, C3’, C5’, C6’), 126.8 (C4’), 123.1 (C3a), 117.7
(C3), 96.9 (C5), 63.4 (OCH3), 56.7 ppm (OCH3); elemental analysis calcd
(%) for C16H14N2O4: C 64.42, H 4.69, N 9.39; found: C 64.10, H 4.92, N
9.52.
À
J=0.7 Hz; H2), 3.96 (s, 3H; OCH3), 3.94 (s, 3H; OCH3), 3.88 (s, 3H; N
CH3), 2.36 ppm (d, 3H, J=0.7 Hz; C3-CH3); 13C NMR (63 MHz, CDCl3):
d=149.8 (C4), 138.5 (C7), 135.4 (C6), 132.3 (C2), 129.4 (C7a), 124.8 (C3a),
À
111.8 (C3), 95.0 (C5), 63.2 (OCH3), 55.3 (OCH3), 35.4 (N CH3), 11.2 ppm
(C3-CH3); elemental analysis calcd (%) for C12H14N2O4: C 57.59, H 5.64,
N 11.19; found: C 57.65, H 5.71, N 10.87.
1-Methyl-4,7-dimethoxy-6-nitro-3-phenylindole (4d): Pale-reddish solid;
yield: 1.450 g, 93%; m.p. 105–1078C; IR (neat): n˜ =1513, 1338 (NO2),
1201 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.56–7.52 (m, 2H;
Ar-H), 7.44–7.30 (m, 4H; Ar-H, H2), 7.16 (s, 1H; H5), 4.15 (s, 3H;
General procedure for indole N-methylation: Preparation of compounds
3 and 4: A 60% suspension of sodium hydride in mineral oil (10 mmol)
was washed twice with dry petroleum ether (10 mL), under an argon at-
mosphere. Dry THF (10 mL) was added, and the resulting suspension
was cooled to 08C, whilst being magnetically stirred. A solution of the
suitable indole substrate (5.0 mmol) in dry THF (50 mL) was added to
this suspension and the mixture was stirred at 08C for 1 h. Methyl iodide
OCH3), 4.05 (s, 3H; OCH3), 3.88 ppm (s, 3H; N CH3); 13C NMR
À
(63 MHz, CDCl3): d=149.5 (C4), 138.7 (C7), 136.7 (C6), 134.3 (C1’), 133.2
(C2), 130.1 (C7a), 129.6, 127.6 (C2’, C3’, C5’, C6’), 126.3 (C4’), 122.5 (C3a),
À
118.5 (C3), 96.5 (C5), 63.6 (OCH3), 55.5 (OCH3), 36.3 ppm (N CH3); ele-
10934
www.chemeurj.org
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10930 – 10939

Vinylation of Nitro-Substituted Indoles, Quinolinones, and Anilides
FULL PAPER
mental analysis calcd (%) for C17H16N2O4: C 65.38, H 5.12, N 8.97;
found: C 65.19, H 4.98, N 8.72.
CDCl3): d=162.0 (C=O), 150.4 (C4), 148.6 (C5), 142.0 (C8), 137.3 (C6),
134.1 (C8a), 124.9 (C3), 115.7 (C4a), 106.8 (C7), 64.0 (OCH3), 57.1 (OCH3),
23.9 ppm (C4-CH3); elemental analysis calcd (%) for C12H14N2O5: C
54.55, H 4.58, N 10.60; found: C 54.27, H 4.54, N 10.73.
Preparation of precursors 7, 8, and 11
5,8-Dimethoxy-1,4-dimethyl-6-nitroquinolin-2
monium bisulphate (770 mg, 2.27 mmol) and 50% potassium hydroxide
solution (820 mg, 20.5 mmol) were added to solution of 11 (3 g,
ACHTUNGTNER(NUNG 1H)one (7): Tetrabutylam-
General procedure for vinylation: A commercial THF solution of the
suitable Grignard reagent (1.5 mmol) was added dropwise to a cooled
(À508C) solution of the adequate substrate (0.5 mmol) in dry THF
(20 mL) under an inert atmosphere. The reaction mixture was stirred at
À508C for 1–5 h, poured onto a saturated NH4Cl aqueous solution
(15 mL) and extracted with ethyl acetate (3ꢄ20 mL). The combined ex-
tracts were dried (anhydrous Na2SO4) and evaporated, and the residue
was purified by fast chromatography on silica gel, eluting with 5:1 petro-
leum ether/ethyl acetate.
a
11.36 mmol) in toluene (100 mL) and the resulting reaction mixture was
stirred for 15 min. Then, methyl iodide (2.1 g, 14.8 mmol) was added and
the reaction mixture was stirred at room temperature for 3 h and water
(30 mL) was then added. The organic layer was dried (anhydrous
Na2SO4) and evaporated, and the residue was washed with acetone.
À
Yield: 2,99 g, 94%; m.p. 1578C; IR (neat): n˜ =1667 (N C=O), 1572, 1324
(NO2), 1283 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3,): d=7.62 (s, 1H;
H7), 6.62 (d, 1H, J=1 Hz; H3), 3.97 (s, 3H; OCH3), 3.88 (s, 3H; OCH3),
1-Methyl-7-methoxy-5-nitro-4-vinylindole (5a): Pale-yellow solid; yield:
110 mg, 95%; m.p. 118–1208C; IR (neat): n˜ =1513, 1330 (NO2),
1215 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.41 (s, 1H; H6),
7.33–7.22 (m, 1H; HC=CH2), 7.06 (d, 1H, J=3.0 Hz; H2), 6.79 (d, 1H,
J=3.0 Hz; H3), 5.69 (s, 1H; HC=CH2), 5.65–5.61 (m, 1H; HC=CH2), 4.11
3.87 (s, 3H; N CH3), 2.67 ppm (d, 3H, J=1 Hz; C4-CH3); 13C NMR
À
(63 MHz, CDCl3): d=162.9 (C2), 148.4 (C5), 146.9 (C8), 144.8 (C4), 138.1
(C8a), 137.0 (C6), 124.6 (C3), 118.4 (C4a), 109.0 (C7), 63.99, 57.2 (2OCH3),
À
36.5 (N CH3), 24.9 ppm (C4-CH3); elemental analysis calcd (%) for
(s, 3H; N CH3), 4.02 ppm (s, 3H; OCH3); 13C NMR (63 MHz, CDCl3):
À
C13H14N2O5: C 56.11, H 5.07, N 10.07; found: C 56.23, H 5.10, N 10.19.
d=146.5 (C7), 140.2 (C5), 132.8 (HC=CH2), 132.1 (C2), 128.9 (C7a), 128.8
N-(2,5-Dimethoxy-4-nitrophenyl)-N-methylacetamide (8a): Nitric acid
(65%, 0.3 mL) was added dropwise to a solution of N-methyl-N-(2,5-di-
methoxyphenyl)acetamide (105 mg, 0.5 mmol) in acetic acid (10 mL) at
08C. The reaction was stirred at 08C for 1 h and at RT for 4 h. Then, the
mixture was cooled at 08C, poured onto cold water (100 mL) and the
yellow solid that precipitated was collected by filtration and washed with
À
(C3a), 123.4 (C4), 119.3 (HC=CH2), 104.3 (C3), 98.9 (C6), 55.8 (N CH3),
36.9 ppm (OCH3); elemental analysis calcd (%) for C12H12N2O3: C 62.06,
H 5.21, N 12.06; found: C 61.78, H 5.32, N 11.74.
AHCTUNGTERG(NNUN E,Z)-1-Methyl-7-methoxy-5-nitro-4-(1-propenyl)indole (5b): Pale-yellow
solid; yield: 108 mg, 88%, corresponding to a Z/E 3:1 mixture; m.p. 93–
958C; IR (neat): n˜ =1518, 1320 (NO2), 1227 cmÀ1 (OCH3); 1H NMR
(250 MHz, CDCl3): Z isomer: d=7.47 (s, 1H; H6), 7.04 (d, 1H, J=
3.0 Hz; H2, partially overlapped with the same signal of the E isomer),
À
water (20 mL). Yield: 117 mg, 92%; m.p. 1258C; IR (neat): n˜ =1667 (N
C=O), 1523, 1346 (NO2), 1210 cmÀ1 (OCH3); 1H-RMN (250 MHz,
CDCl3): d=7.52 (s, 1H; H3), 6.98 (s, 1H; H6), 3.94 (s, 3H; OCH3), 3.88
(s, 3H; OCH3), 3.19 (s, 3H; N CH3), 1,86 ppm (s, 3H; CH3); 13C-RMN
(63 MHz, CDCl3): d=170.6 (C=O), 148.3 (C5), 147.5 (C2), 138.1 (C4),
6.84 (dq. 1H, J=11.2, 1.5 Hz; HC=CH CH3), 6.47 (d, 1H, J=3.0 Hz;
À
À
À
H3), 5.98 (dq, 1H, J=11.2, 6.8 Hz; HC=CH CH3), 4.10 (s, 3H; N-CH3),
À
À
137.8 (C1), 114.7 (C3), 109.2 (C6), 57.1 (OCH3), 56.2 (OCH3), 35.9 (N
4.02 (s, 3H; OCH3), 1.50 ppm (dd, 3H, J=6.8, 1.5 Hz; HC=CH CH3); E
isomer: d=7.37 (s, 1H; H6), 7.01 (d, 1H, J=3.0 Hz; H2, partially over-
lapped with the same signal of the Z isomer), 6.98 (dq, 1H, J=15.8,
À
CH3), 21.6 ppm (CO CH3); elemental analysis calcd (%) for
C11H14N2O5: C 51.97, H 5.55, N 11.02; found: C 51.60, H 5.32, N 10.81.
À
1.5 Hz; HC=CH CH3, partially overlapped with the H2 signal), 6,73 (d,
N-(3-Methoxy-4-nitrophenyl)-N-methylacetamide (8b): Nitric acid (65%,
1.8 mL) was added dropwise to a solution of N-(3-methoxyphenyl)aceta-
mide (500 mg, 3.03 mmol) in acetic acid (15 mL) at 08C. The reaction
was stirred at 08C for 1 h and at RT for 4 h. Then, the mixture was
cooled at 08C, poured onto cold water (100 mL) and extracted with ethyl
acetate (3ꢄ50 mL). The combined extracts were dried (anhydrous
Na2SO4), evaporated, and the residue was purified by fast chromatogra-
phy on silica gel, eluting with a 1:1 petroleum ether/ethyl acetate mixture,
affording 380 mg (60%) of N-(3-methoxy-4-nitrophenyl)acetamide. A so-
lution of this compound (130 mg, 0.72 mmol) in THF (15 mL) was added
to a suspension of NaH (83 mg, 2.07 mmol), previously washed with dry
petroleum ether, in THF (10 mL) at 08C under an argon atmosphere and
stirred at 08C for 1 h. Then, methyl iodide (257 mg, 1.82 mmol) was
added and the reaction was allowed to warm to RT for 4 h. The mixture
was cooled at 08C, poured onto cold water (10 mL), and extracted with
ethyl acetate (3ꢄ30 mL). The combined extracts were dried (anhydrous
Na2SO4), evaporated, and the residue was washed with hexane. Yellow
solid; yield: 120 mg, 75%; m.p. 78–808C; IR (neat): n˜ =1663 (C=O),
1517, 1348 (NO2), 1238 cmÀ1 (OCH3); 1H-RMN (250 MHz, CDCl3): d=
7.91 (d, 1H, J=8.5 Hz; H5), 6.97 (m, 1H; H2), 6.89 (dd, 1H, J=8.5,
À
1H, J=3.0 Hz; H3), 6.15 (dq, 1H, J=15.8, 6.5 Hz; HC=CH CH3), 4.09
À
(s, 3H; N CH3), 4.01 (s, 3H; OCH3), 2.02 ppm (dd, 3H, J=6.5, 1.5 Hz;
HC=CH-CH3); 13C NMR (63 MHz, CDCl3): Z isomer: d=145.9 (C7),
140.3 (C5, overlapped with the same signal of the E isomer), 131.8 (C2),
131.2 (C7a, overlapped with the same signal of the E isomer), 129.2 (C3a),
À
À
127.4 (HC=CH CH3), 125.3 (HC=CH CH3), 122.1 (C4, overlapped with
the same signal of the E isomer), 104.7 (C3), 98.8 (C6, overlapped with
the same signal of the E isomer), 55.7 (OCH3, overlapped with the same
À
signal of the E isomer), 36.6 (N-CH3), 15.1 ppm (HC=CH CH3); E
isomer: d=145.8 (C7), 140.3 (C5, overlapped with the same signal of the
Z isomer), 131.7 (C2), 131.2 (C7a, overlapped with the same signal of the
À
Z isomer), 129.0 (C3a), 128.0 (HC=CH CH3), 126.2 (HC=CH-CH3), 122.1
(C4, overlapped with the same signal of the Z isomer), 104.4 (C3), 98.8
(C6, overlapped with the same signal of the Z isomer), 55.7 (OCH3, over-
lapped with the same signal of the Z isomer), 36.7 ppm (N-CH3), 18.9
(HC=CH CH3); elemental analysis calcd (%) for C13H14N2O3: C 63.41,
H 5.69, N 11.38; found: C 63.80, H 6.00, N 11.04.
À
1-Methyl-4-(2-methyl-1-propenyl)-7-methoxy-5-nitroindole (5c): Pale-
yellow solid; yield: 125 mg, 96%; m.p. 116–1188C; IR (neat): n˜ =1518,
1320 (NO2), 1227 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.41 (s,
1H; H6), 7.03 (d, 1H, J=3.0 Hz; H2), 6.58–6.56 (m, 1H; HC=CACHTUNGTRENNUNG(CH3)2),
6.43 (d, 1H, J=3.0 Hz; H3), 4.09 (s, 3H; N CH3), 4.01 (s, 3H; OCH3),
À
2.0 Hz; H6), 3.87 (s, 3H; OCH3), 3.31 (s, 3H; N CH3), 2.02 ppm (brs,
3H; CO CH3); 13C-RMN (63 MHz, CDCl3): d=169.8 (CO), 153.7 (C3),
À
À
À
149.4 (C1), 137.8 (C4), 126.8 (C5, C6), 111.9 (C2), 56.6 (OCH3), 37.2 (N
CH3), 29.5 ppm (CO CH3); elemental analysis calcd (%) for
À
2.01 (d, 3H, J=1.3 Hz; HC=C
N
C10H12N2O4: C 53.57, H 5.39, N 12.49; found: C 53.94, H 5.76, N 12.22.
CACTHNGUTERNNUG
(CH3)2; 13C NMR (63 MHz, CDCl3): d=145.7 (C7), 14.5(C5), 136.1
(HC=C
(HC=C
(HC=C
ACHTUNGTRENNUNG
5,8-Dimethoxy-4-methyl-6-nitroquinolin-2ACTHNUTRGNE(NUG 1H)one (11): Nitric acid (65%
AHCTUNGTRENNUNG
12.5 mL) was added dropwise to a solution of 5,8-dimethoxy-4-methyl-
quinolin-2(1H)one (5 g, 22.8 mmol) in acetic acid (40 mL) at 08C, and
the reaction mixture was stirred for 1 h at room temperature. Then, the
reaction was poured onto ice water (200 mL) and the yellow solid that
precipitated was collected by filtration and washed with water. Yield:
N
ACHTUNGTRENNUNG
for C14H16N2O3: C 64.61, H 6.15, N 10.76; found: C 64.60, H 6.61, N
10.33.
1,2-Dimethyl-4-isopropenyl-7-methoxy-5-nitroindole (5d): Pale-yellow
solid; yield: 86 mg, 70%; m.p. 38–408C; IR (neat): n˜ =1518, 1320 (NO2),
1260 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.36 (s, 1H; H6),
6.36 (d, 1H, J=0.8 Hz; H3), 5.32–5.30 (m, 1H; H2C=C-CH3), 4.90–4.88
À
6.5 g, 100%; m.p. 2618C; IR (neat): n˜ =3600 (NH), 1664 (N C=O), 1564,
1352 (NO2), 1255 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.55 (s,
1H; H7), 6.60 (d, 1H, J=0.9 Hz; H3), 4.06 (s, 3H; OCH3), 3.91 (s, 3H;
OCH3), 2.73 ppm (d, 3H, J=0.9 Hz; C4-CH3); 13C NMR (63 MHz,
À
(m, 1H; H2C=C-CH3), 4.01 (s, 3H; OCH3), 4.00 (s, 3H; N CH3), 2.41 (d,
Chem. Eur. J. 2009, 15, 10930 – 10939
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10935

J. C. Menꢀndez et al.
3H, J=0.8 Hz; C2-CH3), 2.17–2.16 ppm (m, 3H; H2C=C-CH3); 13C NMR
(63 MHz, CDCl3): d=145.2 (C7), 142.7 (C2), 142.2 (H2C=C-CH3), 139.9
(C2), 131.9 (C7a), 128.3 (C3a), 127.0 (C4), 113.9 (H2C=C-CH3), 102.6 (C3),
(250 MHz, CDCl3): Z isomer: d=7.44 (s, 1H; H6), 6.80 (dq, 1H, J=11.2,
À
1.5 Hz; HC=CH CH3), 6.26 (d, 1H, J=0.8 Hz; H3), 5.95 (dq, 1H, J=
À
À
11.2, 6.8 Hz; HC=CH CH3), 4.01–3.99 (m, 6H; OCH3; N CH3, over-
lapped with the same signal of the E isomer), 2.42 (d, 3H, J=0.8 Hz; C2-
CH3, overlapped with the same signal of the E isomer), 1.50 ppm (dd,
À
98.4 (C6), 55.7 (OCH3), 30.9 (NCH3), 23.3 (H2C=C CH3), 12.8 ppm (C2-
CH3); elemental analysis calcd (%) for C14H16N2O3: C 64.60, H 6.20, N
10.76; found: C 65.03, H 5.95, N 11.00.
À
3H, J=6.8, 1.5 Hz; HC=CH CH3); E isomer: d=7.35 (s, 1H; H6), 6.94
À
(dq, 1H, J=15.8, 1.5 Hz; HC=CH CH3), 6.52 (d, 1H, J=0.8 Hz; H3),
1,3-Dimethyl-7-methoxy-5-nitro-4-vinylindole (5e): Yellow solid; yield:
111 mg, 90%; m.p. 113–1158C; IR (neat): n˜ =1516, 1322 (NO2),
1220 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.30 (dd, 1H, J=
17.6, 11.2 Hz; HC=CH2), 7.28 (s, 1H; H6), 6.81 (brs, 1H; H2), 5.55 (dd,
1H, J=11.2, 1.7 Hz; HC=CH2), 5.21 (dd, 1H, J=17.6, 1.7 Hz; HC=CH2),
À
6.10 (dq, 1H, J=15.8, 6.5 Hz; HC=CH CH3), 4.01–3.99 (m, 6H; OCH3;
N CH3, overlapped with the same signal of the Z isomer), 2.42 (d, 3H,
À
J=0.8 Hz; C2-CH3, overlapped with the same signal of the Z isomer),
2.02 ppm (dd, 3H, J=6.5, 1.5 Hz; HC=CH CH3); 13C NMR (63 MHz,
À
À
CDCl3): Z isomer: d =145.2 (C7), 139.9 (C5), 139.5 (C2, C7a), 128.3 (C3a),
4.02 (s, 3H; N CH3), 3.99 (s, 3H; OCH3), 2.28 ppm (d, 3H, J=0.8 Hz;
C3-CH3); 13C NMR (63 MHz, CDCl3): d=145.9 (C7), 140.5 (C5), 132.2
(HC=CH2), 131.3 (C2), 128.9 (C7a), 126.9 (C3a), 124.3 (C4), 119.3 (HC=
CH2), 114.0 (C3), 98.6 (C6), 55.7 (N-CH3), 36.4 (OCH3), 13.9 ppm (C3-
CH3); elemental analysis calcd (%) for C13H14N2O3: C 63.41, H 5.69, N
11.38; found: C 63.89, H 6.06, N 11.04.
127.1 (HC=CH CH3), 125.5 (HC=CH-CH3), 121.0 (C4), 103.5 (C3), 98.6
À
(C6, overlapped with the same signal of the E isomer), 55.7 (OCH3, over-
À
lapped with the same signal of the E isomer), 32.7 (N CH3, overlapped
À
with the same signal of the E isomer), 15.1 (HC=CH CH3), 12.9 ppm
(C2-CH3); E isomer: d=145.1 (C7), 139.4 (C5), 135.2 (C2), 130.8 (HC=
À
CH-CH3), 128.4 (C3a), 126.3 (HC=CH CH3), 122.4 (C4), 103.3 (C3), 98.6
(C6, overlapped with the same signal of the Z isomer), 55.7 (OCH3, over-
ACHTUNGTRENNUNG(E,Z)-1,3-Dimethyl-7-methoxy-5-nitro-4-(1-propenyl)indole (5 f): Yellow
solid; yield 118 mg, 90%, corresponding to a Z/E 3/1 mixture; m.p. 89–
918C; IR (neat): n˜ =1518, 1320 (NO2), 1227 cmÀ1 (OCH3); 1H NMR
(250 MHz, CDCl3): Z isomer: d=7.30 (s, 1H; H6), 6.86 (dq, 1H, J=11.2,
1.5 Hz; HC=CH-CH3, partially overlapped with the same signal of the E
isomer), 6.79 (brs, 1H; H2, overlapped with the same signal of the E
À
lapped with the same signal of the Z isomer), 32.7 (N CH3 overlapped
with the same signal of the Z isomer), 18.9 (HC=CH CH3), 12.8 ppm
(C2-CH3); elemental analysis calcd (%) for C14H16N2O3: C 64.61, H 6.15,
N 10.77; found: C 65.00, H 6.53, N 10.46.
À
À
isomer), 5.90 (dq, 1H, J=11.2, 6.8 Hz; HC=CH-CH3), 4.02 (s, 3H; N
CH3), 3.99 (s, 3H; OCH3), 2.29 (d, 3H, J=0.8 Hz; C3-CH3), 1.40 ppm
(dd, 3H, J=6.8, J=1.5 Hz; HC=CH-CH3); E isomer: d=7.25 (s, 1H;
1,2-Dimethyl-4-(2-methyl-1-propenyl)-7-methoxy-5-nitroindole
Yellow solid; yield: 123 mg, 90%, corresponding to a Z/E 3:1 mixture;
m.p. 124–1268C; IR (neat): n˜ =1518 (NO2), 1297 cmÀ1 (OCH3); 1H NMR
(5j):
À
H6), 6.91 (dq, 1H, J=15.8, 1.7 Hz; HC=CH CH3, partially overlapped
with the same signal of the Z isomer), 6.79 (brs, 1H; H2, overlapped with
the same signal of the Z isomer), 5.59 (dq, 1H, J=15.8, 6.5 Hz; HC=CH-
(250 MHz, CDCl3): d=7.39 (s, 1H; H6), 6.55 (brs, 1H; HC=CACHTUNGTRENNUNG(CH3)2),
À
6.22 (s, 1H; H3), 4.00 (m, 6H; OCH3, N CH3), 2.41 (s, 3H; C2-CH3), 2.01
(s, 3H; HC=C(CH3)2), 1.47 ppm (s, 3H; HC=C
G
N
À
CH3), 4.00 (s, 3H; N CH3), 3.97 (s, 3H; OCH3), 2.25 (d, 3H, J=0.8 Hz;
(63 MHz, CDCl3): d=145.0 (C7), 140.2 (C5), 139.3 (C2), 135.7 (HC=C-
(CH3)2), 128.8 (C7a), 128.3 (C3a), 122.1 (C4), 120.0 (HC=C(CH3)2), 103.5
(C3), 98.5 (C6), 55.7 (OCH3), 32.7 (N CH3), 25.5 (HC=C(CH3)2), 20.1
(HC=C(CH3)2), 12.9 ppm (C2-CH3); elemental analysis calcd (%) for
C3-CH3), 1.94 ppm (dd, 3H, J=6.5, 1.7 Hz; HC=CH CH3); 13C NMR
À
A
ACHTUNGTRENNUNG
(63 MHz, CDCl3): Z isomer: d=145.7 (C7), 141.1 (C5), 130.9 (C2), 128.6
(C7a), 127.7 (HC=CH-CH3), 127.3 (C3a), 125.3 (HC=CH-CH3), 122.2 (C4),
114.3 (C3), 98.5 (C6, overlapped with the same signal of the E isomer),
À
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
C15H18N2O3: C 65.69, H 6.56, N 10.21; found: C 65.32, H 6.91, N 10.45.
À
55.6 (OCH3, overlapped with the same signal of the E isomer), 36.3 (N
CH3, overlapped with the same signal of the E isomer), 14.1 (HC=CH-
CH3), 12.5 ppm (C3-CH3); E isomer: d=145.5 (C7), 140.9 (C5), 131.0
1,2-Dimethyl-7-methoxy-5-nitro-4-styrylindole (5k): Yellow solid; yield:
147 mg, 91%; m.p. 136–1388C; 1H NMR (250 MHz, CDCl3): d=7.73 (d,
À
1H, J=16.3 Hz; CH=CH-C6H5,), 7.64–7.60 (m, 2H; H2’,H6’), 7.45 (s,
À
(HC=CH-CH3), 130.6 (C2), 130.1 (C7a), 128.9 (C3a), 125.1 (HC=CH
CH3), 124.9 (C4), 114.3 (C3), 98.5 (C6, overlapped with the same signal of
À
1H; H6), 7.46–7.33 (m, 2H; H3’, H4’, H5’), 7.01 (d, 1H, J=16.3 Hz; CH=
CH-C6H5,), 6.64 (d, 1H, J=0.8 Hz; H3), 4.03 (s, 3H; OCH3), 4.02 (s, 3H;
the Z isomer), 55.6 (OCH3, overlapped with the same signal of the Z
isomer), 36.3 (N CH3, overlapped with the same signal of the Z isomer),
18.3 (HC=CH-CH3), 13.8 ppm (C3-CH3); elemental analysis calcd (%)
for C14H16N2O3: C 64.41, H 6.15, N 10.77; found: C 64.09, H 6.29, N
10.46.
N CH3), 2.43 ppm (d, 3H, J=0.8 Hz; C2-CH3,); 13C NMR (63 MHz,
À
À
CDCl3): d=145.4 (C7), 140.0 (C5), 139.9 (C2), 137.3 (C1’), 133.6 (-CH=
CH-C6H5), 129.0 (C7a), 128.5 (C3, C5’), 127.9 (C3a), 127.8 (C4’), 126.6 (C2,
À
À
C6’), 124.8 ( CH=CH C6H5), 121.8 (C4), 103.3 (C3), 98.9 (C6), 55.7
À
(OCH3), 32.8 (N CH3), 12.9 ppm (C2-CH3); IR (neat): n˜ =1514,
1,3-Dimethyl-4-(2-methyl-1-propenyl)7-methoxy-5-nitroindole
(5g):
1299 cmÀ1 (NO2, OCH3); elemental analysis calcd (%) for C19H18N2O3: C
70.80, H 5.60, N 8.69; found: C 71.40, H 5.61, N 8.47.
Yellow solid; yield: 129 mg, 94%; m.p. 71–738C; IR (neat): n˜ =1520,
1330 (NO2), 1227 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.27 (s,
1,3-Dimethyl-7-methoxy-5-nitro-4-styrylindole (5l): Yellow solid; yield:
125 mg, 90%; m.p. 135–1378C; IR (neat): n˜ =1517, 1319 (NO2),
1229 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.68 (d, 1H, J=
1H; H6), 6.77 (brs, 1H; HC=CACTHUNTRGNE(GNU CH3)2), 6.55 (brs, 1H; H2), 4.01 (s, 3H;
À
N CH3), 3.98 (s, 3H; OCH3), 2.23 (s, 3H; C3-CH3), 1.94 (s, 3H; HC=C-
(CH3)2), 1.36 ppm (s, 3H; HC=C
U
À
À
16.3 Hz; CH=CH C6H5), 7.57–7.54 (m, 2H; H2’, H6’), 7.44–7.30 (m, 4H;
d=145.6 (C7), 141.2 (C5), 135.5 (HC=C
ACHTUNGTRENNUNG
H6, H3’, H4’, H5’), 6.84 (brs, 1H, H2), 6.50 (d, 1H, -CH=CH-C6H5, J=
127.9 (C3a), 123.6 (C4), 119.8 (HC=CACTHUNGTRENNNUG
À
À
16.3 Hz), 4.05 (s, 3H; N CH3), 4.02 (s, 3H; OCH3), 2.26 ppm (d, 3H, J=
(OCH3), 36.3 (N CH3), 25.0 (HC=C
12.5 ppm (C3-CH3); elemental analysis calcd (%) for C15H18N2O3: C
65.69, H, 6.57, N 10.21; found: C 65.60, H 6.61, N 10.02.
G
ACHTUNGTRENNUNG
0.8 Hz; C3-CH3); 13C NMR (63 MHz, CDCl3): d=146.0 (C7), 140.8 (C5),
137.0 (C1’), 134.2 (-CH=CH-C6H5), 131.5 (C2), 129.2 (C7a), 128.6 (C3’, C5’),
À
À
127.7 (C4’), 127.6 (C3a), 126.5 (C2, C6’), 124.0 (C4), 123.7 ( CH=CH
1,2-Dimethyl-7-methoxy-5-nitro-4-vinylindole (5h): Yellow solid; yield:
117 mg, 95%; m.p. 118–1208C; IR (neat): n˜ =1515, 1315 (NO2),
À
C6H5), 114.3 (C3), 98.9 (C6), 55.8 (OCH3), 36.5 (N CH3), 14.1 ppm (C3-
1297 cmÀ1 1H NMR (250 MHz, CDCl3): d=7.39 (s, 1H; H6), 7.33–7.22
;
CH3); elemental analysis calcd (%) for C19H18N2O3: C 70.80, H 5.60, N
8.69; found: C 70.80, H 5.62, N 8.36.
(m, 1H; HC=CH2), 6.58 (s, 1H; H3), 5.66 (s, 1H; HC=CH2), 5.62–5.59
À
(m, 1H; HC=CH2), 4.02, 4.01 (2s, 6H; N CH3, OCH3), 2.42 ppm (s, 3H;
1-Methyl-4-methoxy-6-nitro-7-vinylindole (6a): Yellow solid; yield:
106 mg, 91%; m.p. 108–1108C; IR (neat): n˜ =1519, 1313 (NO2),
C2-CH3); 13C NMR (63 MHz, CDCl3): d=145.6 (C7), 139.9 (C5), 135.7
(HC=CH2), 133.2 (C2), 129.5 (C7a), 127.9 (C3a), 124.2 (C4), 118.9 (HC=
1233 cmÀ1
;
1H NMR (250 MHz, CDCl3): d=7.33 (dd, 1H, J=17.5,
À
CH2), 103.7 (C3), 98.8 (C6), 56.1 (OCH3) 32.8 (N CH3), 12.9 ppm (C2-
CH3); (OCH3); elemental analysis calcd (%) for C13H14N2O3: C 63.41, H
5.69, N 11.38; found: C, 63.08, H 5.42, N 11.64.
11.0 Hz; CH=CH2), 7.14 (s, 1H; H5), 7.12 (d, 1H, J=3.0 Hz; H2), 6.65 (d,
1H, J=3.0 Hz; H3), 5.62 (dd, 1H, J=11.0, 1.5 Hz; CH=CH2), 5.28 (dd,
À
1H, J=17.5, 1.5 Hz; CH=CH2), 4.01 (s, 3H; OCH3), 3.90 ppm (s, 3H; N
CH3); 13C NMR (63 MHz, CDCl3): d=151.0 (C4), 143.0 (C6), 134.1 (C2),
133.0 (C7a), 131.0 (CH=CH2), 123.9 (C3a), 121.0 (CH=CH2), 115.0 (C7),
ACHTUNGTRENNUNG(E,Z)-1,2-Dimethyl-7-methoxy-5-nitro-4-(1-propenyl)indole (5i): Yellow
solid; yield: 118 mg, 91%, corresponding to a Z/E 3:1 mixture; m.p. 97–
998C; IR (neat): n˜ =1518, 1318 (NO2), 1220 cmÀ1 (OCH3); 1H NMR
99.0 (C3), 95.9 (C5), 55.0 (OCH3), 38.0 ppm (N CH3); (OCH3); elemental
À
10936
www.chemeurj.org
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10930 – 10939

Vinylation of Nitro-Substituted Indoles, Quinolinones, and Anilides
FULL PAPER
analysis calcd (%) for C12H12N2O3: C 62.10, H 5.20, N 12.05; found: C
62.36, H 4.95, N 11.80.
ACHTUNGTRENNUNG
A
(6b):
Yellow
solid; yield: 122 mg, 99%, corresponding to a E/Z 1.3:1 mixture; m.p.
80–828C; IR (neat): n˜ =1518, 1311 (NO2), 1230 cmÀ1 (OCH3); 1H NMR
(250 MHz, CDCl3): E isomer: d=7.11 (d, 1H, J=3.2 Hz; H2), 7.08 (s,
À
HC=CH CH3), 6.81 (d, 1H, J=0.9 Hz; H2), 5.61 (dq, 1H, J=15.8,
À
À
6.6 Hz; HC=CH CH3), 3.94 (s, 3H; OCH3), 3.78 (s, 3H; N CH3), 2.43
À
(d, 3H, J=0.9 Hz; C3-CH3), 1.93 ppm (dd, 3H, J=6.6, 1.7 Hz; HC=CH
CH3); Z isomer: d=7.09 (s, 1H; H5), 6.85–6.81 (m, 1H; HC=CH-CH3),
6.83 (d, 1H, J=0.9 Hz; H2), 5.98 (dq, 1H, J=11.0, 6.8 Hz; HC=CH
À
1H; H5), 6.87 (m, 1H; HC=CH CH3), 6.61 (d, 1H, J=3.2 Hz; H3), 5.65
À
(dq, 1H, J=15.9, 6.6 Hz; HC=CH CH3), 3.99 (s, 3H; OCH3), 3.87 (s,
À
À
À
3H; N CH3), 1.94 ppm (dd, 3H, J=6.6, 1.7 Hz; HC=CH CH3);
isomer: d=7.15 (s, 1H; H5), 7.09 (d, 1H, J=3.2 Hz; H2), 6.92 (m, 1H;
Z
À
CH3), 3.96 (s, 3H; OCH3), 3.81 (s, 3H; N CH3), 2.45 (d, 3H, J=0.9 Hz;
C3-CH3), 1.37 ppm (dd, 3H, J=6.8, 1.7 Hz; HC=CH CH3); 13C NMR
À
À
HC=CH CH3), 6.64 (d, 1H, J=3.2 Hz; H3), 6.01 (dq, 1H, J=11.0,
(63 MHz, CDCl3): E isomer: d=152.9 (C4), 144.3 (C6), 134.8 (C7a), 132.2
(HC=CH-CH3), 131.3 (HC=CH CH3), 123.9 (C2), 122.3 (C3a, overlapped
with the same signal of the Z isomer), 114.7 (C7, overlapped with the
same signal of the Z isomer), 111.0 (C3, overlapped with the same signal
of the Z isomer), 95.3 (C5), 55.4 (OCH3), 37.8 (N-CH3), 18.3 (HC=CH
CH3), 11.6 ppm (C3-CH3, overlapped with the same signal of the Z
isomer); Z isomer: d=153.1 (C4), 144.2 (C6), 134.5 (C7a), 132.3 (HC=CH-
CH3), 129.5 (HC=CH-CH3), 124.0 (C2), 122.3 (C3a, overlapped with the
same signal of the E isomer), 114.7 (C7, overlapped with the same signal
of the E isomer), 111.0 (C3, overlapped with the same signal of the E
À
6.8 Hz; HC=CH-CH3), 4.01 (s, 3H; OCH3), 3.90 (s, 3H; N CH3),
1.40 ppm (dd, 3H, J=6.8, 1.7 Hz; HC=CH CH3); 13C NMR (63 MHz,
CDCl3): E isomer: d=151.0 (C4), 144.5 (C6), 134.1 (C7a, overlapped with
the same signal of the Z isomer), 133.7 (C2), 131.6 (HC=CH-CH3), 123.6
(C3a), 123.3 (HC=CH-CH3), 114.8 (C7), 98.6 (C3, overlapped with the
À
À
À
À
same signal of the Z isomer), 95.6 (C5), 55.4 (OCH3), 38.1 (N CH3),
18.3 ppm (CH3); Z isomer: d=151.2 (C4), 144.4 (C6), 134.1 (C7a, over-
lapped with the same signal of the E isomer), 133.7 (C2), 129.7 (HC=
À
À
CH CH3), 123.6 (C3a), 123.7 (C3, HC=CH CH3), 112.5 (C7), 98.6 (C3,
overlapped with the same signal of the
E isomer), 95.8 (C5), 55.4
À
isomer), 95.5 (C5), 55.4 (OCH3), 36.6 (N-CH3), 14.2 (HC=CH CH3),
À
(OCH3), 36.9 (N CH3), 14.2 ppm (CH3); elemental analysis calcd (%)
for C13H14N2O3: C 63.41, H 5.69, N 11.38; found: C 63.68, H 5.84, N
11.04.
11.6 ppm (C3-CH3, overlapped with the same signal of the E isomer); ele-
mental analysis calcd (%) for C14H16N2O3: C 64.61, H 6.15, N 10.77;
found: C 64.29, H 6.48, N 10.52.
4-Methoxy-1-methyl-7-(2-methyl-1-propenil)-6-nitroindole (6c): Brown
solid; yield: 122 mg, 94%; m.p. 458C; IR (neat): n˜ =1500, 1333 (NO2),
1230 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.11 (s, 1H; H5),
7.09 (d, 1H, J=3.0 Hz; H2), 6.62 (d, 1H, J=3.0 Hz; H3), 6.58–6.57 (m,
À
4-Methoxy-1,3-dimethyl-7-(2-methyl-1-propenyl)-6-nitroindol
Yellow solid; yield: 99 mg, 72%; m.p. 55–578C; IR (neat): n˜ =1516, 1329
(NO2), 1236 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.06 (s, 1H;
H5), 6.82 (brs, 1H; H2), 6.56 (brs, 1H; HC=CACTHUNGTRNEUNG(CH3)2), 3.96 (s, 3H;
OCH3), 3.77 (s, 3H; N CH3), 2.44 (brs, 3H; C3-CH3), 1.95 (brs, 3H;
(CH3)2), 1.36 ppm (brs, 3H; HC=C
CDCl3): d=152.9 (C4), 145.0 (C6), 137.7 (HC=C
132.4 (C2), 124.3 (C3a), 118.1 (HC=C
(6h):
1H; HC=CACHTUNGTRENNUNG(CH3)2), 3.99 (s, 3H; OCH3), 3.85 (s, 3H; N CH3), 1.96 (d,
À
3H, J=1.3 Hz; HC=C
(CH3)2); 13C NMR (63 MHz, CDCl3): d=151.0 (C4), 144.6 (C6), 137.8
(HC=C(CH3)2), 134.1 (C7a), 133.6 (C2), 123.2 (C3a), 117.9 (HC=C(CH3)2),
113.9 (C7), 98.6 (C3), 95.7 (C5), 55.5 (OCH3), 36.7 (N-CH3), 24.9 (-CH3),
19.2 ppm (HC=C(CH3)2); elemental analysis calcd (%) for C14H16N2O3:
ACHTUNGTRENNUNG(CH3)2), 1.37 ppm (d, 3H, J=1.0 Hz; HC=C-
HC=C
G
U
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
C 64.61, H 6.15, N 10.77; found: C 65.00, H 6.34, N 10.43.
C15H18N2O3: C 65.69, H 6.57, N 10.21; found: C 65.30, H 6.21, N 9.94.
4-Methoxy-1-methyl-6-nitro-7-styrylindol (6d): Brown solid; yield:
151 mg, 98%; m.p. 141–1438C; IR (neat): n˜ =1520, 1324 (NO2),
1232 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.65 (d, 1H, J=
4-Methoxy-1,3-dimethyl-7-(2-methyl-1-propenyl)-6-nitroindol (6i): Yellow
solid; yield: 93 mg, 71%; m.p. 75–778C; IR (neat): n˜ =1510, 1316 (NO2),
1
À
1232 cmÀ1; H NMR (250 MHz, CDCl3): d=7.07 (s, 1H; H5), 6.85 (d, 1H,
16.3 Hz; HC=CH C6H5), 7.57–7.53 (m, 2H; Ph), 7.46–7.29 (m, 3H; Ph),
J=0.8 Hz; H2), 5.39–5.37 (m, 1H; H2C=C-CH3), 5.01–5.00 (m, 1H; H2C=
7.24 (s, 1H; H5), 7.15 (d, 1H, J=3.0 Hz; H2), 6.69 (d, 1H, J=3.0 Hz; H3),
À
À
C-CH3), 3.96 (s, 3H; OCH3), 3.90 (s, 3H; N CH3), 2.45 (d, 3H, J=
6.53 (d, 1H, J=16.3 Hz; HC=CH C6H5), 4.04 (s, 3H; OCH3), 3.86 ppm
(s, 3H; N CH3); 13C NMR (63 MHz, CDCl3): d=151.9 (C4), 144.7 (C6),
À
À
0.8 Hz; C3-CH3), 2.31 ppm (t, 3H, J=1.2 Hz; H2C=C CH3); 13C NMR
À
À
(63 MHz, CDCl3): d=153.1 (C4), 143.4 (C6), 140.1 (H2C=C CH3), 133.3
(C7a), 132.3 (C2), 122.8 (C3a), 118.8 (C7), 117.7 (H2C=C CH3), 111.4 (C3),
95.4 (C5), 55.7 (OCH3), 35.9 (N-CH3), 26.2 (H2C=C CH3), 11.7 ppm (C3-
CH3); (OCH3); elemental analysis calcd (%) for C14H16N2O3: C 64.61, H
6.15, N 10.77; found: C 65.01, H 6.06, N 10.87.
136.9 (C1’), 135.3 (C2), 134.8 (C7a), 134.7 (HC=CH C6H5), 129.0, 128.8
(C2’, C3’, C5’, C6’), 128.9 (C4’), 124.4 (C3a), 122.5 (HC=CH C6H5), 115.3
(C7), 99.5 (C3), 96.6 (C5), 56.1 (OCH3), 39.0 ppm (N CH3); elemental
analysis calcd (%) for C18H16N2O3: C 70.12, H 5.19, N 9.09; found: C
70.52, H 5.36, N 8.91.
À
À
À
À
4-Methoxy-1,2-dimethyl-6-nitro-7-vinylindol (6j): Dark-green solid; yield:
118 mg, 96%; m.p. 65–678C; IR (neat): n˜ =1515, 1315 (NO2), 1234 cmÀ1
(OCH3); H NMR (250 MHz, CDCl3): d=7.30 (dd, 1H, J=17.5, 11.0 Hz;
4-Methoxy-1-methyl-7-isopropenyl-6-nitroindol (6e): Brown solid; yield:
92 mg, 75%; m.p. 87–898C; IR (neat): n˜ =1522, 1315 (NO2), 1223 cmÀ1
(OCH3); 1H NMR (250 MHz, CDCl3): d=7.14–7.12 (m, 2H; H2, H5),
6.66 (d, 1H, J=3.0 Hz; H3), 5.42–5.40 (m, 1H; H2C=C-CH3), 5.04–5.03
1
HC=CH2), 7.14 (s, 1H; H5), 6.44 (s, 1H; H3), 5.59 (dd, 1H, J=11.0,
À
À
1.5 Hz; HC=CH2), 5.23 (dd, 1H, J=17.5, 1.5 Hz; HC=CH2), 3.99 (s, 3H;
(m, 1H; H2C=C CH3), 4.01 (s, 3H; OCH3), 3.99 (s, 3H; N CH3),
OCH3), 3.77 (s, 3H; N CH3), 2.43 ppm (s, 3H; C2-CH3); 13C NMR
2.27 ppm (dd, 3H, J=1.3, 0.8 Hz; H2C=C CH3); 13C NMR (63 MHz,
À
À
(63 MHz, CDCl3): d=152.7 (C4), 143.1 (C6), 132.8 (C2), 132.2 (C7a), 131.7
(HC=CH2), 123.5 (C3a), 121.0 (C7), 119.3 (HC=CH2), 112.2 (C3), 96.0
(C5), 56.7 (OCH3), 37.5 (N-CH3), 12.2 ppm (C2-CH3); elemental analysis
calcd (%) for C13H14N2O3: C 63.41, H 5.69, N 11.38; found: C 63.21, H
5.32, N 11.09.
CDCl3): d=151.2 (C4), 139.7 (C6, H2C=C-CH3), 133.8 (C2), 123.8 (C7a),
118.9 (C3a), 117.7 (H2C=C CH3), 98.9 (C3), 95.8 (C5), 55.6 (OCH3), 36.1
(N CH3), 25.9 ppm (H2C=C CH3); elemental analysis calcd (%) for
C13H14N2O3: C 63.41, H 5.69, N 11.38; found: C 63.70, H 5.82, N 11.15.
À
À
À
4-Methoxy-1,3-dimethyl-6-nitro-7-vinylindol (6 f): Pale-brown solid; yield:
117 mg, 95%; m.p. 57–598C; IR (neat): n˜ =1515, 1315 (NO2), 1234 cmÀ1
(OCH3); H NMR (250 MHz, CDCl3): d=7.30 (dd, 1H, J=17.5, 11.0 Hz;
HC=CH2), 7.07 (s, 1H; H5), 6.83 (s, 1H; H2), 5.59 (dd, 1H, J=11.0,
1.5 Hz; HC=CH2), 5.23 (dd, 1H, J=17.5, 1.5 Hz; HC=CH2), 3.96 (s, 3H;
AHCTUNGTERG(NNUN E,Z)-4-Methoxy-1,2-dimethyl-6-nitro-7-(1-propenyl)indole (6k): Brown
1
solid; yield: 126 mg, 97%, corresponding to a E/Z 1.3:1 mixture; m.p.
68–708C; IR (neat): n˜ =1517, 1326 (NO2), 1225 cmÀ1 (OCH3); 1H NMR
(250 MHz, CDCl3): E isomer: d=7.10 (s, 1H; H5), 6.93–6.88 (m, 1H;
À
À
OCH3), 3.81 (s, 3H; N CH3), 2.44 ppm (d, 3H, J=0.8 Hz; C3-CH3);
HC=CH CH3), 6.42 (d, 1H, J=0.8 Hz; H3), 5.61 (dq, 1H, J=15.9,
13C NMR (63 MHz, CDCl3): d=153.3 (C4), 144.0 (C6), 134.4 (C7a), 132.4
(HC=CH2), 131.4 (C2), 122.5 (C3a), 120.4 (HC=CH2), 115.0 (C7), 111.2
(C3), 95.4 (C5), 55.5 (OCH3), 38.0 (N-CH3), 11.6 ppm (C3-CH3); elemental
analysis calcd (%) for C13H14N2O3: C 63.41, H 5.69, N 11.38; found: C
63.26, H 5.90, N 11.04.
6.6 Hz; HC=CH CH3), 3.98 (s, 3H; OCH3), 3.75 (s, 3H; N CH3), 2.43
(d, 3H, J=0.8 Hz; C2-CH3, partially overlapped with the same signal of
À
À
À
the Z isomer), 1.94 ppm (dd, 3H, J=6.6, 1.8 Hz; HC=CH CH3); Z
isomer: d=7.16 (s, 1H; H5), 6.97–6.94 (m, 1H; HC=CH-CH3), 6.44 (d,
1H, J=0.9 Hz; H3), 5.99 (dq, 1H, J=11.0, 6.8 Hz; HC=CH-CH3), 4.00 (s,
Chem. Eur. J. 2009, 15, 10930 – 10939
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10937

J. C. Menꢀndez et al.
(NO2), 1296 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.45 (s, 1H;
H7), 7.30 (dd, 1H, J=17.6, 11.1 Hz; HC=CH2), 6.61 (s, 1H; H3), 5.42 (d,
1H, J=11.1 Hz; HC=CH2), 5.07 (d, 1H, J=17.6 Hz; HC=CH2), 3.97 (s,
À
3H; OCH3), 3.80 (s, 3H; N CH3), 2.44 (d, 3H, J=0.9 Hz; C2-CH3, parti-
ally overlapped with the same signal of the E isomer), 1.39 ppm (dd, 3H,
J=6.8, 1.7 Hz; HC=CH CH3); 13C NMR (63 MHz, CDCl3): E isomer:
d=150.1 (C4), 143.9 (C6, overlapped with the same signal of the Z
isomer), 141.3 (C2), 135.0 (C7a), 131.2 (HC=CH-CH3), 124.3 (HC=CH
CH3), 114.7 (C7, C3a), 98.2 (C3, overlapped with the same signal of the Z
isomer), 96.0 (C5), 55.5 (OCH3), 33.9 (NCH3), 18.4 (HC=CH-CH3),
13.6 ppm (C2-CH3, overlapped with the HC=CH CH3 signal of the Z
isomer); Z isomer: d=150.3 (C4), 143.9 (C6, overlapped with the same
signal of the E isomer), 141.4 (C2), 134.5 (C7a), 129.4 (HC=CH CH3),
122.7 (HC=CH CH3), 112.3 (C7, C3a), 98.2 (C3, overlapped with the same
signal of the E isomer), 96.2 (C5), 55.5 (OCH3), 32.7 (N-CH3), 13.6 (HC=
CH CH3, overlapped with the C2 CH3 signal of the E isomer), 14.2 ppm
(C2 CH3); elemental analysis calcd (%) for C14H16N2O3: C 64.61, H 6.15,
N 10.77; found: C 64.55, H 6.33, N 10.57.
À
3H; OCH3), 3.83 (s, 3H; N CH3), 2.48 ppm (s, 3H, C4-CH3); 13C NMR
À
À
(63 MHz, CDCl3): d=163.0 (C2), 148.2 (C8), 147.9 (C4), 136.3 (C6), 134.7
(HC=CH2, H8a), 126.8 (C4a), 125.4 (C3), 123.5 (C5), 120.7 (HC=CH2),
À
107.3 (C7), 56.9 (OCH3), 37.1 (N CH3), 27.1 ppm (C4-CH3); elemental
À
analysis calcd (%) for C14H14N2O4: C 61.31, H 5.14, N 10.21; found: C
61.43, H 5.25, N 10.09.
À
AHCTUNGTERG(NNUN E,Z)-8-Methoxy-1,4-dimethyl-6-nitro-5-(1-propenyl)quinolin-2(1H)one
À
(12b): Yield: 133 mg, 92% corresponding to a E/Z 1.3:1 mixture; IR
(neat): n˜ =1662 (N C=O), 1515, 1335 (NO2), 1271 cmÀ1 (OCH3);
À
À
À
1H NMR (250 MHz, CDCl3): E isomer: d=7.41 (s, 1H; H7), 6.83–6.81
À
À
(m, 1H; HC=CH CH3), 6.60–6.58 (m, 1H; H3, overlapped with the same
signal of the Z isomer), 5.38 (dd, 1H, J=15.8, 6.6 Hz; HC=CH-CH3),
4-Methoxy-1,2-dimethyl-7-isopropenyl-6-nitroindol (6l): Yellow solid;
yield: 111 mg, 85%; m.p. 155–1578C; IR (neat): n˜ =1515, 1314 (NO2),
1219 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.13 (s, 1H; H5),
À
3.95 (s, 3H; OCH3), 3.81 (s, 3H; N CH3), 2.42 (d, 3H, J=1.0 Hz; C4-
CH3), 1.85 ppm (dd, 3H, J=6.6, 1.8 Hz; HC=CH-CH3); Z isomer: d=
7.44 (s, 1H; H7), 6.89–6.85 (m, 1H; HC=CH-CH3), 6.60–6.58 (m, 1H; H3,
overlapped with the same signal of the E isomer), 5.84 (dd, 1H, J=11.2,
À
6.46 (d, 1H, J=0.8 Hz; H2), 5.41–5.38 (m, 1H; H2C=C CH3), 5.03–5.01
À
À
(m, 1H; H2C=C CH3), 3.99 (s, 3H; OCH3), 3.87 (s, 3H; N CH3), 2.45
À
À
6.9 Hz; HC=CH CH3), 3.97 (s, 3H; OCH3), 3.84 (s, 3H; N CH3), 2.47
(d, 3H, J=1.0 Hz; C4-CH3), 1.28 ppm (dd, 3H, J=6.9, 1.8 Hz; HC=CH
À
(d, 3H, J=0.8 Hz; C2-CH3), 2.34 ppm (t, 3H, J=1.1 Hz; H2C=C CH3);
C NMR (63 MHz, CDCl3): d=150.9 (C4), 143.4 (C6), 142.1 (H2C=C
CH3), 140.8 (C2), 134.2 (C7a), 123.6 (C3a), 119.1 (C7), 117.9 (H2C=C
CH3), 98.7 (C3), 96.4 (C5), 56.0 (OCH3), 32.2 (N CH3), 26.5 (H2C=C
CH3), 14.1 ppm (C2-CH3); elemental analysis calcd (%) for C14H16N2O3:
C 64.61, H 6.15, N 10.77; found: C 64.34, H 6.14, N 10.45.
À
13
À
CH3); 13C NMR (63 MHz, CDCl3): E isomer: d=163.1 (C2), 148.3 (C8),
147.9 (C4, overlapped with the same signal for the Z isomer), 145.9 (C6),
136.3 (C8a),131.8 (HC=CH-CH3), 127.5 (HC=CH-CH3), 126.5 (C4a, over-
lapped with the same signal for the Z isomer), 125.3 (C3), 123.9 (C5),
107.3 (C7), 56.9 (OCH3, overlapped with the same signal for the Z
À
À
À
4-Methoxy-1,2-dimethyl-7-(2-methyl-1-propenyl)-6-nitroindol
(6m):
À
À
isomer), 37.1 (N CH3), 26.8 (C4-CH3), 18.9 ppm (HC=CH CH3);
isomer: d=163.0 (C2), 148.2 (C8), 147.9 (C4, overlapped with the same
signal for the E isomer), 146.1 (C6), 136.1 (C8a), 129.9 (HC=CH CH3),
127.0 (HC=CH CH3), 126.5 (C4a, overlapped with the same signal for the
E isomer), 125.3 (C3), 124.0 (C5), 107.5 (C7), 56.9 (OCH3, overlapped
with the same signal for the E isomer), 37.2 (N CH3), 26.4 (C4-CH3),
14.2 ppm (HC=CH CH3); elemental analysis calcd (%) for C15H16N2O4:
Z
Yellow solid; yield: 105 mg, 81%; m.p. 98–1008C; IR (neat): n˜ =1515,
1302 (NO2), 1230 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.13 (s,
1H; H5), 6.61–6.59 (m, 1H; HC=CACHTNUGRTNEUNG(CH3)2), 6.43 (d, 1H, J=0.8 Hz; H3),
À
À
À
3.99 (s, 3H; OCH3), 3.77 (s, 3H; N CH3), 2.43 (d, 3H, J=0.8 Hz; C2-
CH3), 1.97 (d, 3H, J=1.3 Hz; HC=C(CH3)2), 1.36 ppm (d, 3H, J=
1.0 Hz; HC=C
(CH3)2); 13C NMR (63 MHz, CDCl3): d=150.1 (C4), 144.0
(C6), 141.4 (HC=C(CH3)2), 137.4 (C2), 134.8 (C7a), 122.5 (C3a), 118.4
(HC=C(CH3)2), 113.6 (C7), 98.1 (C3), 96.1 (C5), 55.5 (OCH3), 32.4 (N
CH3), 24.8 (HC=C(CH3)2), 19.2 (HC=C(CH3)2), 13.7 ppm (C2-CH3); ele-
AHCTUNGTRENNUNG
À
ACHTUNGTRENNUNG
À
ACHTUNGTRENNUNG
C 62.49, H 5.59, N 9.72; found: C 62.84, H 5.88, N 9.55; MS (EI): m/z
À
(%): 288 (39) [M]+, 245 (100) [MÀ43]+.
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
8-Methoxy-1,4-dimethyl-6-nitro-5-styrylquinolin-2(1H)one (12c): Yield:
mental analysis calcd (%) for C15H18N2O3: C 65.69, H 6.57, N 10.21;
found: C 65.75, H 6.47, N 9.94.
À
132 mg, 75%; m.p. 98–1008C; IR (neat): n˜ =1662 (N C=O), 1519, 1329
(NO2), 1289 cmÀ1 (OCH3); 1H NMR (250 MHz, CDCl3): d=7.66 (s, 1H;
A
(6n):
À
H7), 7.62 (d, 1H, J=16.2 Hz; HC=CH Ph), 7.53–7.31 (m, 5H; Ph), 6.95
Dark-red solid; yield: 158 mg, 98%, corresponding to a E/Z 1.3:1 mix-
ture; m.p. 53–558C; IR (neat): n˜ =1517, 1340 (NO2), 1203 cmÀ1 (OCH3);
1H NMR (250 MHz, CDCl3): E isomer: d=7.47–7.41 (m, 2H; Ph, over-
lapped with the same signal of the Z isomer), 7.33–7.21 (m, 3H; Ph, over-
lapped with the same signal of the Z isomer), 7.18 (s, 1H; H5, overlapped
with the same signal of the Z isomer), 7.05 (s, 1H; H2, overlapped with
À
(s, 1H; H3), 6.37 (d, 1H, J=16.3 Hz; HC=CH Ph), 4.09 (s, 3H; OCH3),
4.07 (s, 3H; N CH3), 2.62 ppm (d, 3H, J=0.9 Hz; C4-CH3); 13C NMR
À
(63 MHz, CDCl3): d=162.5 (C2), 147.7 (C8), 147.6 (C4), 144.9 (C6), 136.5
(C8a), 136.1 (C1’), 134.6 (HC=CH-Ph), 128.8, 126.6 (C2’, C3’, C5’, C6’), 128.4
(C4’), 128.0 (C4a), 126.0 (C5), 125.0 (HC=CH Ph), 124.9 (C3), 107.1 (C7),
56.5 (OCH3), 36.6 (N CH3), 26.6 ppm (C4-CH3); elemental analysis calcd
(%) for C20H18N2O4: C 68.56, H 5.18, N 8.00; found: C 68.26, H 5.02, N
7.65.
À
À
À
the same signal of the Z isomer), 6.92–6. 91 (m, 1H; HC=CH CH3), 5.59
À
(dq, 1H, J=15.8, 6.6 Hz; HC=CH-CH3), 4.04 (s, 3H; N CH3), 3.75 (s,
À
À
3H; O CH3), 1.86 ppm (dd, 3H, J=6.6, 1.7 Hz; HC=CH CH3);
Z
N-(2-Methoxy-4-nitro-5-vinylphenyl)-N-methylaniline
(13a):
Yellow
isomer: d=7.47–7.41 (m, 2H, Ph, overlapped with the same signal of the
E isomer), 7.33–7.21 (m, 3H; Ph, overlapped with the same signal of the
E isomer), 7.18 (s, 1H; H5, overlapped with the same signal of the E
isomer), 7.05 (s, 1H; H2, overlapped with the same signal of the E
isomer), 6.97–6.95 ppm (m, 1H; HC=CH-CH3), 5.94 (dq, 1H, J=11.0,
solid; 79 mg: 63%; m.p. 55–578C; IR (neat): n˜ =1538, 1312 (NO2),
1217 cmÀ1 (OCH3); 1H-RMN (250 MHz, CDCl3): d=7.60 (s, 1H; H3);
7.45 (dd, 1H, J=17.2, 10.8 Hz; HC=CH2); 6.54 (s, 1H; H6); 5.62 (dd, 1H,
J=17.2, 1.3 Hz; HC=CH2); 5.40 (dd, 1H, J=10.8, 1.3 Hz; HC=CH2);
À
5.04 (brs, 1H; NH), 3.94 (s, 3H; OCH3); 3.00 ppm (d, 3H, J=5.2 Hz; N
À
À
6.8 Hz; HC=CH CH3), 3.82 (s, 3H; N CH3), 3.74 (s, 3H; OCH3),
CH3); 13C-RMN (63 MHz, CDCl3): d=144.9. (C2), 144.1 (C1), 135.5
(HC=CH2), 131.6 (C4), 130.8 (C5), 116.5 (HC=CH2), 106.4 (C3), 105.8
13
À
1.35 ppm (dd, 3H, J=6.8, 1.7 Hz; HC=CH CH3); C NMR (63 MHz,
CDCl3): E isomer: d =152.6 (C4), 149.4 (C6), 138.6 (C7a), 134.2 (C1’),
133.2 (C2), 130.1 (HC=CH-CH3), 129.7, 127.5 (C2’, C3’, C5, C6’), 126.3
À
(C6), 55.9 (OCH3), 29.6 ppm (N CH3); elemental analysis calcd (%) for
C10H12N2O3: C 57.68, H 5.81, N 13.45; found: C 57.42, H 5.59, N 13.23.
À
(HC=CH CH3), 123.7 (C4’, overlapped with the same signal of the Z
isomer), 119.8 (C3a), 117.5 (C3), 112.3 (C7), 96.4 (C5), 55.3 (OCH3), 37.3
(N-CH3), 14.4 ppm (HC=CH-CH3); Z isomer: d=152.4 (C4), 144.6 (C6),
136.0 (C7a), 134.8 (C1’), 133.1 (C2) 131.8 (HC=CH-CH3), 129.6, 127.6 (C2’,
C3’, C5, C6’), 126.1 (HC=CH-CH3), 123.7 (C4’, overlapped with the same
signal of the E isomer), 122.5 (C3a), 118.5 (C3), 114.6 (C7), 96.3 (C5), 55.5
N-(4-Nitro-3-vinylphenyl)-N-methylaniline (13b): Yellowish/green solid;
71 mg: 64%; m.p. 66–688C; IR (neat): n˜ =1579, 1309 cmÀ1 (NO2); 1H-
RMN (500 MHz, CDCl3): d=8.07 (d, 1H, J=9.0 Hz; H5), 7.40 (dd, 1H,
J=17.2, 10.8 Hz; CH=CH2), 6.58 (d,1H, J=2,6 Hz; H2), 6.51 (dd, 1H,
J=9.0, 2.6 Hz; H6), 5.62 (dd,1H, J=17.2, 1.0 Hz; CH=CH2), 5.42 (dd,1H,
J=10.8, 1.0 Hz; CH=CH2), 4.50 (brs, 1H; NH), 2.97 ppm (d, 3H, J=
À
(OCH3), 36.3 (N CH3), 18.4 ppm (HC=CH-CH3); elemental analysis
2.8 Hz; N CH3); 13C-RMN (125 MHz, CDCl3): d=153.2 (C1), 137.8 (C3),
137.1 (C4), 135.5 (CH=CH2), 127.9 (C5), 117.3 (CH=CH2), 110.5 (C2, C6),
calcd (%) for C19H18N2O3: C 70.79, H 5.63, N 8.69; found: C 70.62, H
6.01, N 8.04.
À
À
8-Methoxy-1,4-dimethyl-6-nitro-5-vinylquinolin-2
129 mg, 94%; m.p. 117–1188C; IR (neat): n˜ =1663 (N C=O), 1524, 1328
G
30.1 ppm (N CH3); elemental analysis calcd (%) for C9H10N2O2: C 60.66,
H 5.66, N 15.72; found: C 60.97, H 5.84, N 15.37.
10938
www.chemeurj.org
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10930 – 10939

Vinylation of Nitro-Substituted Indoles, Quinolinones, and Anilides
FULL PAPER
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We thank Dr. J. D. Sꢂnchez for some preliminary experiments. Financial
support from the MICINN (grant no. CTQ2006–10930), UCM-CAM
(Grupos de Investigaciꢅn, grant no. 920234), and CAM (predoctoral con-
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Received: May 18, 2009
Published online: September 10, 2009
Chem. Eur. J. 2009, 15, 10930 – 10939
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10939