On the reactivity of some 2-methyleneindolines with β-nitroenamines, α-nitroalkenes, and 1,2-diaza-1,3-butadienes

Article abstract of DOI:10.1016/j.tet.2006.04.027

A study of the behaviour of some electron-rich 2-methyleneindolines (1-3) with different electron-poor reagents (formation of new carbon-carbon and nitrogen-carbon bonds) has furnished interesting results from both synthetic and the mechanistic viewpoints

Full text of DOI:10.1016/j.tet.2006.04.027

Tetrahedron 62 (2006) 6420–6434
On the reactivity of some 2-methyleneindolines with
b-nitroenamines, a-nitroalkenes, and 1,2-diaza-1,3-butadienes
a
a
b
Orazio A. Attanasi,a, Gianfranco Favi, Paolino Filippone, Cristina Forzato,
*
Gianluca Giorgi,c Stefano Morganti,d Patrizia Nitti,b Giuliana Pitacco,b Egon Rizzato,d
Domenico Spinellid and Ennio Valentinb,
*
a
`
Istituto di Chimica Organica, Universita degli Studi di Urbino ‘Carlo Bo’, Via Sasso 75, 61029 Urbino, Italy
b
`
Dipartimento di Scienze Chimiche, Universita di Trieste, Via Licio Giorgieri 1, 34127 Trieste, Italy
`
c
Centro Interdipartimentale di Analisi e Determinazioni Strutturali, Universita degli Studi di Siena, Via Aldo Moro, 53100 Siena, Italy
d
`
Dipartimento di Chimica Organica ‘A. Mangini’, Universita degli Studi di Bologna, Via S. Giacomo 11, 40126, Bologna, Italy
Received 11 January 2006; revised 21 March 2006; accepted 6 April 2006
Available online 11 May 2006
Abstract—A study of the behaviour of some electron-rich 2-methyleneindolines (1–3) with different electron-poor reagents (formation of
new carbon–carbon and nitrogen–carbon bonds) has furnished interesting results from both synthetic and the mechanistic viewpoints.
Enamines 1–3 have been reacted with the b-nitroenamines 4–7 (reaction CeCl3$7H2O promoted), giving the polymethine dyes 14–23.
The same bases 1–3 have been nitroalkylated with the nitroolefins 8–10, furnishing the indolines 24–32, and the diastereoselectivity of
the reaction has been thoroughly investigated. The most unexpected results derived from the first example of reaction of Fischer’s bases
with 1,2-diaza-1,3-butadienes. In fact, with 11–13, the ‘unknown’ indoline spirodihydropyrroles 33–40 were formed. Their structures
were unambiguously assigned, and we determined, as an example, that of 33 by X-ray analysis.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
a class of photochromic organic compounds that have been
extensively studied since the first report by Fischer and
Hirshberg.8 The photochromism of spiropyran9 and spiro-
oxazine6,9c,10 is based on the reversible colour change
between the closed spiro-structure and the open planar mero-
cyanine structure. Permanent open forms of spirooxazines
can be also synthesized.11
Fischer’s base1 1 (1,3,3-trimethyl-2-methyleneindoline) has
been frequently used in dye chemistry for the synthesis of
polymethine dyes, a class of compounds that contain an elec-
tron donor and an electron acceptor at the opposite ends of
the methine chain.2 Thus, chiral monomethine cyanine
dyes,3 chiral arylazomethyleneindoline dyes4 and chiral tri-
methine cyanine dyes2c were synthesized using chiral 2-
methyleneindolines as key intermediates.
In accordance with previous considerations and in the frame-
work of our interest on the use of nitroalkenylation reactions
in organic synthesis, we have addressed our attention to the
behaviour of bases 1–3 (electron-rich substrates) with the
b-nitroenamines 4–712–16 (electron-poor reagents) (Fig. 1)
with the aim of obtaining new polymethine dyes. For the
sake of comparison and continuing our studies on nitroalky-
lation reactions16 of 2-methyleneindolines, we investigated
the reactivity of bases 1–3 with the a-nitroalkenes 8–
10,17–18 also to verify the diastereoselectivity of this reaction
on the chiral racemic substrates 2 and 3. Furthermore, for the
first time, the study of the reactivity study of nucleophiles
such as 1–3 has been extended to the 1,2-diaza-1,3-butadi-
enes 11–13,19 electrophiles that, because of their polyfunc-
tionalized structure, could show unexpected development
in the reaction.
Also interesting are the reactions of Fischer’s base with
2-hydroxybenzaldehyde derivatives5 and 1-nitroso-2-hy-
droxyaryl derivatives,6 which afford spiropyran and
[1,4]-spirooxazine derivatives, respectively, whereas [1,2]-
spirooxazine derivatives can be obtained using nonaromatic
nitrosohydroxy compounds.7 These spirocompounds are
Keywords: Polymethine cyanine dyes; Nitroalkenylation; Nitroalkylation;
Diastereoselection; Spiroindolinedihydropyrroles.
* Corresponding authors. Tel.: +39 0722 303442; fax: +39 0722 303441
(O.A.A.); tel.: +39 040 5583917; fax: +39 040 5583903 (E.V.); e-mail
addresses: attanasi@uniurb.it; valentin@dsch.units.it
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.027

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
6421
NO2
R1
NO2
R
MeO2C
NO2
NO2
SCH3
N
N
N
N
R2
N
COR1
O
Me
4: R1 = H
5: R1 = Me
6: R1 = Ph
7
8: R2 = Me
9: R2 = Ph
10
11: R1 = NH2
12: R1 = OMe
13: R1 = O-t-Bu
1: R = Me
2: R = Et
3: R = Ph
Figure 1. 2-Methyleneindolines 1–3, b-nitroenamines 4–7, nitroolefins 8–10 and 1,2-diaza-1,3-butadienes 11–13.
2. Results and discussion
nucleophilic (in 1–3) and electrophilic (in 4–6 or in 7, see
subsequently) characters, respectively. In such a way com-
pounds containing the interesting diene system having at the
two ends an electron-donating and an electron-withdrawing
group have been built-up, that is, polymethine dye systems.
2.1. Reactivity of indolines with b-nitroenamines
2.1.1. Nitroalkenylation reactions of 2-methyleneindo-
lines 1–3 with nitroenamines 4–6. The enamines 1–3
(2 equiv) reacted with the nitroenamines 4–6 (1 equiv) in di-
chloromethane, in the presence of 1 equiv of CeCl3$7H2O,20
to yield the corresponding nitroalkenylated products 14–22
(Scheme 1), with formation of a new carbon–carbon bond
between two sp2-hybridized carbon atoms, showing
The presence of Ce(III) chloride promotes the reaction, with
time varying from 4 to 15 days. Yields of purified products
ranged between 26% and 56% (Table 2). The geometry of
the two conjugated double bonds in the products 16–22(com-
pounds 14 and 15 were already known16) was established as
(10E,20E) by difference NOE measurements performed on 16,
19, 20, 21 and 22 (Table 1) and by comparison of the reso-
nances of their vinyl protons (Table 2). In all compounds ex-
amined, irradiation of the methyl group on nitrogen caused
the enhancement of the H-10 vinyl proton signal, whereas
by irradiating the H-20 vinyl proton either the methyl group
(in 16, 19, 20, 21, and 22) or the methylene group of the ethyl
chain (in 19) was enhanced, thus demonstrating the s-trans
geometry of the butadiene moiety.
R
N
Me
O
1–3
.
CeCl3 7H2O
N
NO2
R1
R
+
THF
NO2
N
Me
R1
2.1.2. Nitroalkenylation reaction of Fischer’s base 1 with
nitroenamine 7. In this case, CeCl3$7H2O alone was not
able to promote the reaction. On the contrary, when a mixture
of CeCl3$7H2O (0.2 equiv) and NaI (0.1 equiv)21 was used,
the nitroalkenylated product 23 was isolated in 10% yield.
The lower yield found in this case, in which the nitroolefin
phenyl ring bears a methylthio group, when compared
with that found for the nitroolefin 6 with the same substrate
(Table 2) would suggest a preferred coordination of cerium
with sulfur, owing to its known great affinity for oxygen
and sulfur. InCl3 was also used as a Lewis acid, however, af-
ter 7 days only traces of the product 23 could be detected in
the 1H NMR spectrum of the crude reaction mixture (Fig. 2).
This result is difficult to explain, as in some cases InCl3
has been found to be more efficient than CeCl3$7H2O.22
When Zn(CF3SO3)2 was used, the same product 23 was
isolated in 30% yield. The ability of zinc triflate to promote
carbon–carbon bond formation in the indole chemistry has
N
O
4–6
NO2
R1
R
N
Me
R
R1
H
14: Me
Me
Me
Et
15:
16:
17:
18:
Me
Ph
H
R
3' NO2
R1
4
2'
1'
5
6
3
2
Et Me
N
Me
19: Et
Ph
H
7
Ph
Ph
Ph
20:
21:
22:
Me
Ph
Scheme 1. Nitroalkenylation products of 2-methyleneindolines 1–3.
Table 1. Difference NOE data for compounds 16, 19, 20, 21, and 22
Compound
Irradiated nucleus:
CH3 at N c.s. (ppm)
Enhanced nucleus:
H-10 c.s. (ppm)
h
Irradiated nucleus:
H-20 c.s. (ppm)
Enhanced nucleus:
CH3 at C-3 c.s. (ppm)
h
10–18%
16
19
3.09
3.09
5.23
5.30
0.14
0.15
8.74
8.71
1.71
1.69
2.31a
1.93
1.93
1.99
0.18
0.12
0.14
0.10
0.13
0.18
H
2'
NO2
R1
R
20
21
22
3.40
3.40
3.20
5.41
5.25
5.20
0.11
0.13
0.16
7.70
7.82
8.07
1'
N
H
Me
H
11–16%
16, 19, 20, 21, 22
Enhancement of the methylene of the ethyl group.
a

6422
O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
Table 2. Reaction times, reaction yields and the most meaningful 1H NMR
data for the nitrodiene derivatives 14–23
bond formation, as evaluated by the (Aj+Bj) parameter25
(0.09, 1.22 and 1.25, respectively).
Product
Reaction
time (d)
Yield
(%)
1H NMR
H-20 ppm,
mult., J (Hz)
It is noteworthy that the position of band 4 was particularly
affected by solvent polarity, being significantly shifted from
434–452 nm in cyclohexane to longer wavelengths (batho-
chromic shift) in acetonitrile (473–489 nm) and in methanol
(477–491 nm). Moreover, for all compounds, in the apolar
solvent cyclohexane, a further intense absorption band
(band 3) appeared around 417–436 nm.
H-10 ppm,
mult., J (Hz)
14
15
16
17
18
19
20
21
22
23
14
14
6
15
4
7
8
4
15
12
56
53
45
38
42
44
31
42
26
30
5.46, d, 13.2
5.30, d, 13.2
5.23, d, 13.5
5.51, d, 13.1
5.34, d, 13.5
5.30, d, 13.5
5.41, d, 12.9
5.25, d, 13.0
5.20, d, 13.2
4.93, d, 13.5
8.38, dd, 13.2, 12.1
8.50, d, 13.2
8.74, d, 13.5
8.34, t, 13.1
8.46, d, 13.5
8.71, d, 13.5
7.70, t, 12.9
7.82, d, 13.0
8.07, d, 13.2
8.74, d, 13.5
2.2. Reactivity of indolines with a-nitroolefins
2.2.1. Nitroalkylation reactions of 2-methyleneindolines
1–3 with a-nitroolefins 8–10. The nitroalkylation reactions
of 2-methyleneindolines 1–3 with the a-nitroolefins 8–10
were performed in diethyl ether and furnished the corre-
sponding products 24–32 (Scheme 2) in good yields, with
the exception of the products derived from 3, which were ob-
tained in a much lower yield. Evidently, the steric hindrance
of the phenyl group greatly affected the approach of the re-
agents. Compound 26 had already been synthesized,16 and it
is included only for comparison.
NO2
SMe
N
Me
23
Figure 2. Compound 23.
already been evidenced to be superior to other heavy-metal
salts and lanthanide salts as well.23
Once more a new carbon–carbon bond between carbon
atoms initially sp2-hybridized is formed, but, in this case,
the absence of a leaving group in 8–10 causes the formation
of an alkenic instead of an alkadienic system.
2.1.3. UV spectra of trimethines 16–23. All the nitrodiene
derivatives 16–23 exhibited an intense absorption band in
the visible region. Their electronic spectra were recorded
(see data in Table 3) in three solvents with very different
properties. In fact, cyclohexane, acetonitrile and methanol
were different from one another, as shown by the values of
their empirical parameters of solvent polarity. They differed
not only in their dielectric properties, evaluated by using the
ENT (that is, the normalized parameter of solvatochromic sol-
vent polarity: 0.006, 0.460 and 0.762, respectively) values,24
but also for their different aptitude to participate in hydrogen
Moreover the higher electrophilic character of 8–10, caused
by the absence of the amino moiety, makes unnecessary the
presence of the Lewis acid promoters.
2.2.2. Reactions of 2-methyleneindolines 1–3 with 1-
nitropropene 8 and b-nitrostyrene 9. The reaction of
Fischer’s base 1 with (E)-1-nitropropene 8 gave compound
24 as a single diastereomer. By contrast, in the reaction of
Table 3. Electronic absorption spectra of compounds 16–23: lmax [nm] (log 3)
Solvent
Band 1
Band 2
Band 3
Band 4
16
17
18
19
20
21
22
23
CH3OH
CH3CN
CyHa
CH3OH
CH3CN
CyHa
CH3OH
CH3CN
CyHa
CH3OH
CH3CN
CyHa
CH3OH
CH3CN
CyHa
CH3OH
CH3CN
CyHa
CH3OH
CH3CN
CyHa
CH3OH
CH3CN
CyHa
208 (4.29)
193 (4.76)
195 (4.65)
209 (3.97)
195 (4.60)
212 (4.01)
209 (4.01)
192 (4.94)
216 (4.15)
208 (4.25)
193 (3.91)
195 (4.68)
208 (4.41)
194 (5.02)
197 (4.66)
207 (4.29)
194 (4.72)
210 (4.21)
209 (4.60)
193 (4.98)
210 (4.49)
209 (4.50)
203 (4.46), 209 (4.47)
201 (4.24), 210 (4.41)
275 (4.12)
277 (4.05)
251 (3.71), 279 (4.09)
277 (3.90)
280 (4.13)
247 (3.68), 276 (3.94)
283 (3.99)
280 (4.35)
248 (4.06), 280 (4.20)
284 (3.95)
276 (4.16)
279 (4.21)
275 (3.94)
277 (4.24)
271 (4.11)
276 (4.28)
280 (4.07)
248 (3.77)
263 (4.12)
490 (4.42)
485 (4.46)
450 (3.94)
483 (4.41)
477 (4.59)
440 (4.26)
490 (4.48)
480 (4.65)
448 (4.53)
491 (4.57)
488 (4.56)
452 (4.46)
477 (4.15)
473 (4.55)
434 (4.45)
483 (4.46)
477 (4.49)
440 (3.85)
487 (4.35)
484 (4.40)
443 (4.13)
489 (4.42)
489 (4.48)
451 (4.36)
434 (3.93)
420 (4.22)
428 (4.51)
436 (4.45)
417 (4.43)
421 (3.86)
429 (4.15)
432 (4.35)
260 (4.17)
254 (3.98)
254 (4.08), 281 (3.97)
259 (4.10), 288 (3.99)
259 (4.09), 281 (3.99)
a
CyH, cyclohexane.

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
6423
R
stereocentre. In fact, the diastereomeric excess (de) was
80% for the reaction of enamine 2, and it was only 50%
for the reaction of the 2-methyleneindoline 3 with the
same a-nitroolefin. The relative stereochemistry of the nitro-
alkyl chain was tentatively assigned as 20R* and 20S* by
N
Me
R1
NO2
R2
R
1-3
Et2O
r.t.
1
analysis of the H NMR data for compounds 30a and 30b
(Fig. 3).
+
N
H
R1
NO2
R2
Me
NO2
Ph
R*
Ph
R*
NO2
2'R*
8-10
2'S*
R
R1
R2
H
H
N
N
24: Me Me
R1
NO2
R2
R
Me
Me
25:
26:
27:
28:
29:
30:
31:
32:
Me
Me
Ph
-(CH2)4-
30a
30b
Et Me
Et Ph
H
H
N
Figure 3. Structures of compounds 30a and 30b.
-(CH2)4-
Me
Et
Me
H
Ph
Ph
Ph
Ph
H
-(CH2)4-
Although a rotation around the C10–C20 single bond is
possible, the average positions of the methyl group and the
nitromethylenic group are influenced differently by the
presence of the phenyl group. Thus, the methyl doublet at
C-20 resonated at 0.50 ppm for the major component 30a
and at 1.04 ppm for the minor component 30b, whereas
the resonances of the respective nitromethylenic protons ap-
peared at 4.19 ppm for 30a, as an AB part of an ABXY3 sys-
tem, and at higher field (3.64 and 3.36 ppm, two double
doublets) for 30b. Therefore, the (3R*,20R*) configuration
was assigned to 30a, for which the methyl group at C-20 is
more shielded by the phenyl group, and the (3R*,20S*) con-
figuration to 30b, for which the nitromethylenic protons are
more shielded. These assignments agree with the R*,Si*
topological approach of a-nitroolefins to the enamines,
and is similar to that proposed by Seebach et al.26 (Fig. 4).
In a similar manner, the diastereomers 27a and 27b were
assigned the (3R*,20R*) and (3R*,20S*) configurations.
Scheme 2. Nitroalkylation products of 2-methyleneindolines 1–3 with
nitroalkenes 8–10.
1 with (E)-b-nitrostyrene 9, two isomers, 25a and 25b, were
obtained in a 9:1 ratio. The E geometry was assigned to com-
pounds 24 and 25a on the basis of NOE measurements. In
fact, irradiation of the respective vinyl protons (3.96 ppm
for 24 and 4.39 ppm for 25a) enhanced the signal of the sin-
glet relative to the methyl group at nitrogen (2.95 ppm for 24
and 3.00 ppm for 25a) for 6% and 13%, respectively. As
a consequence, 25b was assigned the Z configuration.
The reactions of 2-methyleneindolines 2 and 3 with 1-nitro-
propene 8 and b-nitrostyrene 9 gave pairs of inseparable dia-
stereomers 27a,b, 28a,b, 30a,b and 31a,b at ratios of 9:1,
3:2, 3:1 and 1:1, respectively (Table 4). The a and b isomers
were assigned the E configuration because the chemical
shifts of their vinyl proton H-10 were practically the same,
differing by 0.01–0.04 ppm. In Table 4 we also report the
chemical shifts of (E)-24, (E)-25a and (Z)-25b. NOE exper-
iments were performed on compounds 24–28, 30 and 31, in
order to confirm their geometries. Irradiation of the nitrogen
methyl group caused enhancement of the respective vinyl
proton signal for amounts ranging from 5% to 13%.
R
R
H
H
H
H
H
R*
N
O2N
R2
R*
R2
N
H
O2N
Me
Me
H
H
more favourable
R*,Si* approach
less favourable
R*,Re* approach
It is interesting to point out that only in the reactions of 2
and 3 with 1-nitropropene 8 it was possible to envisage
a 1,4-asymmetric induction for the formation of the new
R2
NO2
R2
NO2
R
R
N
N
H
H
Me
Me
Table 4. Relative yields and chemical shift values of vinyl proton signals for
compounds 24, 25, 27, 28, 30 and 31
Figure 4. The proposed topological approach.
Entry
Product
Yield (%)
H-10 (ppm)
In the reaction of 2-methyleneindoline 3 with b-nitrostyrene
9, the isomers 31a and 31b were formed in a 1:1 ratio. Since
the nitromethylenic protons resonated as two double dou-
blets at 4.56 and 4.48 ppm for 31a and at 4.14 and
3.60 ppm for 31b, owing to the C.I.P. configurational rules,
in this case the (3R*,20S*) configuration was assigned to
31a and the (3R*,20R*) configuration to 31b, the former
being generated by an R*,Si* approach and the latter by an
R*,Re* approach. In this case the two approaches were
equally probable.
1
2
(E)-24
100
90
10
90
10
60
40
75
25
50
50
3.96
4.39
4.25
4.02
4.03
4.46
4.47
3.99
3.95
4.40
4.36
(E)-25a
(Z)-25b
(E)-27a
(E)-27b
(E)-28a
(E)-28b
(E)-30a
(E)-30b
(E)-31a
(E)-31b
3
4
5
6

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O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
R
2.2.3. Reactions of 2-methyleneindolines 1–3 with nitro-
cyclohexene 10. The reaction of Fischer’s base 1 with nitro-
cyclohexene 10 gave two diastereomeric Michael-type
adducts 26a and 26b, both of which were in E geometry
and differed in the orientation of the nitro group.16
N
R1OC
R
Me
1-3
N
N
THF
r.t.
+
H
In the reaction of 2-methyleneindoline 2 with nitrocyclohex-
ene 10, two isomers, 29a and 29b, were formed in a 3:1 ratio.
The same E geometry was assigned to both diastereomers by
comparison of their 1H NMR data with those of the known
compounds 26.16 Since the axial and equatorial orientations
of the nitro group were easily recognizable from the positions
and patterns of the respectivenitromethine proton signals, the
cis and trans geometries were assigned to 29a and 29b, re-
spectively. In fact, in the cis isomer 29a, the equatorial nitro-
methine proton resonated at lower field than the same proton
in the trans isomer 29b (4.62 ppm vs 4.22 ppm). The two sig-
nals also exhibited different patterns: a double triplet with
J1¼J2¼4.3, J3¼8.8 Hz and WH¼16 Hz for 29a and a multi-
plet with WH¼26 Hz for 29b, in accordance with equatorial
and axial orientations, respectively, of the nitromethine pro-
tons. On standing, the cis diastereomer 29a slowly converted
into the more stable trans isomer 29b, thus confirming the
assignments made.
COOMe
R1OC
N
Me
N
N
CO2Me
11-13
R
R1
NH2
33: Me
NHCOR1
34: Me OMe
R
4
7
35: Me O-t-Bu
3a
5'
N
NH2
5
6
36: Et
3
2
2'
3'
37: Et
OMe
4'
N
7a
38: Et O-t-Bu
CO2Me
NH2
40: Ph O-t-Bu
39: Ph
Me
Scheme 3. The spirocompounds 33–40.
(Fig. 5).27 Indoline spirodihydropyrroles have not been re-
ported in the literature, and only few cases of spiroindole-
pyrrolidinones are known.28 Interestingly, whereas the H
1
The 1H NMR analysis of the crude reaction mixture obtained
from the enamine 3 and nitrocyclohexene 10 indicated the
presence of three diastereomers of E configuration: cis-32a,
trans-32b and cis-32c in 60%, 25% and 15% yields, respec-
tively. Unfortunately, purification by column chromato-
graphy did not allow a complete separation of the products.
In fact, cis-32a transformed in large amount into trans-32b,
whereas cis-32c converted completely into trans-32d.
and 13C NMR spectra of 33 in CDCl3 showed the presence
of a single product, in DMSO-d6 each peak was split into
two signals, thus indicating the presence of two conformers
a and b in a 60:40 ratio. They remained stable even when
the temperature was increased. The relative signals did not
coalesce even at 110 ꢀC. However, after recovering the prod-
uct from DMSO-d6, its spectrum again in CDCl3 showed the
signals of the parent isomer. DIFNOE measurements were
performed on the two conformers 33a and 33b with the
aim of understanding the origin of this isomerism.
Irradiating the methyl group linked to nitrogen in the major
component 33a at 2.60 ppm an enhancement was observed
for the signal of the NH group at 6.94 ppm (4%), whereas,
in the minor component 33b, the same signal (at 7.22 ppm)
was enhanced by irradiating the methyl group at C-3 at
1.23 ppm. These results suggest that, in the major isomer
33a, the NH group of the chain pointed towards the nitrogen
of the indole moiety, as shown by the X-ray structure,
whereas, in the minor isomer, the same group pointed to-
wards C-3 of the indole moiety. This could be consistent
with an inversion (flip-flap) at the pyrroline nitrogen.
The cis configuration assigned to 32a and 32c on the basis of
their lower thermodynamic stability was confirmed by an
analysis of the signals of their respective nitromethine pro-
tons when they were compared with those of the correspond-
ing trans isomers 32b and 32d. In fact, the nitromethine
protons resonated at 4.48 ppm (WH¼18.4 Hz) for 32a and
at 4.48 ppm (WH¼18.4 Hz) for 32c, whereas the same signal
appeared at 4.10 ppm (WH¼30.0 Hz) for 32b and at
3.94 ppm (WH¼29.0 Hz) for 32d.
In accordance with the above stereochemical considerations
and the type of proposed topological approach described in
Figure 4, the same (3R*,20R*) configuration was assigned to
32a and 32b, whereas the (3R*,20S*) configuration was
assigned to 32c and 32d.
2.3. Reactions of 2-methyleneindolines 1–3 with 1,2-
diaza-1,3-butadienes 11–13
The reactions between the indolines 1–3 and the 1,2-diaza-
1,3-butadienes 11–1319a,b were performed in THF at room
temperature, which produced the tricyclic addition com-
pounds 33–40 in good yields (81–96%) (Scheme 3) with for-
mation of two new bonds (carbon–carbon and nitrogen–
carbon, respectively).
The interesting spiro-structure of compound 33 has been
unambiguously determined by X-ray diffraction study
Figure 5. X-ray structure of compound 33.

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
Table 5. Chemical compositions of compounds 33–40
6425
The structure of the minor isomer 33b was optimized with
the Cornell version of the Amber force field,29 which
showed a relative energy difference of 4 kcal/mol with
respect to 33a. In the invertomer 33b, the proximity of the
NH group to the methyl group at C-3 is evident. No other
rotamer of 33a would account for the NOE effect observed
for 33b. Figure 6 presents a better representation of the
two isomers showing the distance between the protons
involved in the NOE effects observed.
Compound
a:b CDCl3
a:b DMSO-d6
33
34
35
36
37
38
39
40
100:0
60:40
60:40
75:25
55:45
60:40
40:60
40:60
60:40
55:45
50:50
60:40
50:50
50:50
65:35
55:45
3. Conclusion
By reaction of 2-methyleneindoline derivatives 1–3 with b-
nitroenamines 4–7, new deeply coloured trimethine dyes
containing the nitro function as the electron-acceptor group
were obtained. These syntheses were promoted by
CeCl3$7H2O, although in most cases long reaction times
were required. Studies on the optical properties of these
dyes are under investigation.
In the nitroalkylation reactions of 1 and 2, (E)-1-nitropropene
8 proved more diastereoselective than (E)-b-nitrostyrene 9,
as it has already been observed for enolates,14a whereas the
nitrocyclohexene 10 was the most diastereoselective. The
nitroalkylation reactions of the 2-methyleneindoline 3 were
less satisfactory as far as yields and diastereoselectivity are
concerned. This was probably due to the severe steric hin-
drance carried on both sides of the enamine system by the
phenyl group.
The reactions of 2-methyleneindolines with 1,2-diaza-1,3-
butadienes 11–13 gave rise to unknown indoline spiropyrro-
lines. It is noteworthy that neither spirotetrahydropyridazines
deriving from the possible [4+2] cycloaddition, nor the
simple Michael addition products were detected. The new
reaction observed provides a route to interesting, partially
reduced benzocondensed pyrrole derivatives that are inter-
mediates in natural product synthesis.28,30 Experiments of
ring opening under thermal and photochemical conditions
are in progress, to verify whether a ring open-chain equilibra-
tion is possible to modulate the absorption wavelength of the
molecules.
4. Experimental
4.1. General
Figure 6. Optimized geometries of 33a and 33b.
NMR analysis of all the other products 34–40 showed that
they were mixtures of isomers a and b even in CDCl3. If
this result can be attributed to the presence of conformers
for compounds 34 and 35, which possess a single stereo-
centre, the same conclusion cannot be drawn immediately
for compounds 36–40, which possess two stereocentres.
However, a comparison between the spectra of the same
spirocompounds in CDCl3 and in DMSO-d6 revealed that
they simply differed in the composition of a and b, as shown
in Table 5. This could suggest that a and b are conformers
and not diastereomers. In that case the preferred approach
of the enamines 2 and 3 onto the 1,2-diaza-1,3-butadienes
would occur from the less sterically demanding side namely
the one that contains the methyl group at C-3.
IR spectra were recorded on a Jasco FT/IR 200 spectropho-
tometer. 1H NMR and 13C NMR spectra were run on a Jeol
EX-400 spectrometer (400 MHz for proton, 100 MHz for
carbon) and a Jeol EX-270 spectrometer (270 MHz for pro-
ton, 68 MHz for carbon), using deuteriochloroform as a sol-
vent and tetramethylsilane as the internal standard. Coupling
constants are given in Hertz. GLC analyses were run on
a Carlo Erba GC 8000 instrument, the capillary column
being OV 1701 (25 mꢁ0.32 mm) (carrier gas He, 40 kPa,
split 1:50). Mass spectra were recorded on an ion trap
FINNIGAN GCQ (70 eV) spectrometer, HRMS were re-
corded on a FINNIGAN MAT95XP apparatus. UV spectra
were recorded on a HELIOS b-UNICAM spectrophoto-
meter. TLCs were performed on PolygramÒ Sil G/UV254

6426
O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
silica gel pre-coated plastic sheets (eluant: light petroleum–
ethyl acetate). Flash chromatography was run on silica gel
230–400 mesh ASTM (Kieselgel 60, Merck). Light petro-
leum refers to the fraction with bp 40–70 ꢀC. All solvents
were distilled over appropriate drying agents and maintained
over molecular sieves. 2,3-Dihydro-2-methylene-1,3,3-tri-
methyl-1H-indole 1, 3-methyl-2-pentanone and trans-
b-nitrostyrene 9 were purchased from Sigma–Aldrich.
Phenylhydrazine was purchased from Carlo Erba; 4-(2-
nitroethenyl)morpholine 4,12 4-(2-nitro-1-propenyl)mor-
pholine 5,13 4-(2-phenylethenyl-2-nitro)morpholine 6,14
1-[(1E)-2-[2-(methylthio)phenyl]-2-nitroethenylpyrrolidine 7,15
3-phenyl-2-butanone,31a 1-nitropropene,17 1-nitrocyclo-
hexene18 and 1,2-diaza-1,3-butadienes 11–1319,32 were syn-
thesized according to the literature.
4.3.2. 3-Phenyl-2-butanone phenylhydrazone (42).31a To
a solution of phenylhydrazine (2.5 ml, 25 mmol) in ethanol
(9 ml) 3-phenyl-2-butanone31a (3.70 g, 25 mmol) was added.
The orange solution obtained was refluxed for 7 h and after
removal of the solvent the phenylhydrazone 42 was obtained
in 91% yield. Mp 70–72 ꢀC; IR (cmꢂ1, Nujol) 3350 (NH),
1
1601 (C]N), 1498 (Ph); H NMR (d, ppm, CDCl3) 7.40–
7.12 (9H, m, Ar-H), 6.84 (1H, t, Ar-H, J¼7.3 Hz), 3.70
(1H, m, CH), 2.05 (1H, s, NH), 1.68 (3H, s, CH3C), 1.51
(3H, d, CH3CH, J¼7.0 Hz); 13C NMR (d, ppm, CDCl3)
148.0 (s), 146.1 (s), 143.8 (s), 129.3 (d), 128.6 (d), 127.8
(d), 126.6 (d), 119.7 (d), 113.1 (d), 48.3 (d, C-3), 18.9 (q,
CH3), 13.6 (q, CH3).
4.3.3. 3-Ethyl-2,3-dimethyl-3H-indole (43).36 To a solution
of 41 (15.02 g, 79.0 mmol) in ethanol (28.8 ml) p-toluenesul-
fonic acid monohydrate (PTSA, 30.43 g, 160.0 mmol) was
added and the mixture refluxed for 5 h. After evaporation
of the solvent the oil obtained was dissolved in CH2Cl2,
washed with a saturated solution of NaHCO3, brine and dried
over anhydrous Na2SO4. Evaporation of the solvent gave
compound 16 as a brown oil in 85% yield. IR (cmꢂ1, film)
4.2. Synthesis of 2-methyleneindoline derivatives 2 and 3
2-Methyleneindoline derivatives 2 and 3 were prepared
according to the procedure of Brunner33 and Ferratini,34 as in-
dicated in Scheme 4. Fischer’s indolization35 of 3-methyl-2-
pentanone phenylhydrazone 41 and 3-phenyl-2-butanone
phenylhydrazone 4231b furnished the corresponding 3H-
indoles 4336 and 4437 that were alkylated with iodomethane
providing salts 452c and 46, respectively. Their treatment
with KOH afforded 3-ethyl-1,3-dimethyl-2-methylene-
indoline 2 and 2-methylene-1,3-dimethyl-3-phenylindoline
3, respectively.
1
1577 (C]N); H NMR (d, ppm, CDCl3) 7.53 (1H, d, Ar-
H, J¼7.7 Hz), 7.29 (1H, t, Ar-H, J¼7.5 Hz), 7.21 (2H, m,
Ar-H), 2.23 (3H, s, CH3C]N), 1.90 (1H, m, HCHCH3),
1.79 (1H, m, HCHCH3), 1.28 (3H, s, CH3C), 0.39 (3H, t,
CH3CH2, J¼7.5 Hz); 13C NMR (d, ppm, CDCl3) 187.0 (s,
C]N), 154.5 (s), 143.4 (s), 127.4 (d), 125.0 (d), 121.4 (d),
119.6 (d), 58.3 (s, C-3), 30.0 (t, CH2CH3), 22.3 (q,
CH3C]N), 15.6 (q, CH3C), 8.4 (q, CH3CH2); HRGC
(OV1701) tR¼13.72 (10 min at 100 ꢀC, 3 ꢀC/min up to
200 ꢀC).
R
R
PTSA, ∆
N
EtOH
N
N
H
41: R = Et
42: R = Ph
43: R = Et
44: R = Ph
4.3.4. 2,3-Dimethyl-3-phenyl-3H-indole (44).37 Com-
pound 44 was obtained in 94% yield following the same pro-
cedure described for the synthesis of 43. Mp, IR and 1H NMR
are in accordance with those reported in the literature.37 13C
NMR (d, ppm, CDCl3) 187.1 (s), 154.5 (s), 146.9 (s), 139.2
(s), 128.9 (d), 128.0 (d), 127.3 (d), 126.1 (d), 125.9 (d),
122.6 (d), 120.1 (d), 61.8 (s), 20.4 (q, CH3), 15.9 (q, CH3).
CH3I
40°C
R
R
KOH, EtOH
r.t., 3h
N+
Me
N
Me
I–
4.3.5. 3-Ethyl-1,2,3-trimethyl-3H-indolium iodide (45).2c
Methyl iodide (12.6 ml, 0.20 mol) was added to compound
43 (11.72 g, 68.0 mmol), and the solution was warmed at
40 ꢀC until a precipitate was formed. The white solid was
filtered and washed with diethyl ether. Compound 45 was
obtained in 72% yield (15.33 g, 49.0 mmol). Mp 240–
242 ꢀC. All spectroscopic data were identical to those re-
ported in the literature.2c
2: R = Et
3: R = Ph
45: R = Et
46: R = Ph
Scheme 4. Synthesis of 2-methyleneindolines 2 and 3.
4.3. Synthesis of substrates
4.3.1. 3-Methyl-2-pentanone phenylhydrazone (41). To
a solution of phenylhydrazine (7.8 ml, 80 mmol) in ethanol
(28.8 ml) 3-methyl-2-pentanone (9.8 ml, 80.0 mmol) was
added. After refluxing the solution for 5 h and evaporation
of the solvent the phenylhydrazone 41 was obtained as a yel-
low oil (99% yield). IR (cmꢂ1, film) 3350 (NH), 1602
4.3.6. 1,2,3-Trimethyl-3-phenyl-3H-indolium iodide (46).
Compound 46 was obtained in 34% yield by the same pro-
cedure described for the synthesis of 45. Mp 227–229 ꢀC;
1
1
(C]N), 1502 (Ph); H NMR (d, ppm, CDCl3) 7.23 (2H, t,
IR (cmꢂ1, Nujol) 1633, 1610, 1590; H NMR (d, ppm,
Ph-H, J¼7.9 Hz), 7.05 (2H, d, Ph-H, J¼8.4 Hz), 6.81 (1H,
t, Ph-H, J¼7.3 Hz), 2.43 (1H, m, CHCH3), 2.13 (1H, s,
NH), 1.82 (3H, s, CH3C), 1.57 (1H, m, HCHCH3), 1.44
(1H, m, HCHCH3), 1.10 (3H, d, CH3CH, J¼7.0 Hz), 0.89
(3H, t, CH3CH2, J¼7.3 Hz); 13C NMR (d, ppm, CDCl3)
146.0 (s, C]N), 129.2 (2d, Ph), 119.7 (d, Ph), 113.2 (2d,
Ph), 43.8 (d, CHCH3), 27.3 (t, CH2CH3), 17.8 (q, CH3),
12.1 (q, CH3), 12.0 (q, CH3).
CDCl3) 7.78 (1H, d, Ar-H, J¼8.0 Hz), 7.64 (1H, t, Ar-H,
J¼7.7 Hz), 7.57 (1H, t, Ar-H, J¼7.5 Hz), 7.41–7.33 (4H,
m, Ar-H), 7.10–7.06 (2H, m, Ar-H), 4.42 (3H, s, CH3N+),
2.94 (3H, s, CH3C]N), 1.25 (3H, s, CH3C); 13C NMR (d,
ppm, CDCl3) 194.6 (s, C-2), 142.3 (s), 142.2 (s), 133.8 (s),
130.6 (d), 129.9 (2d), 129.7 (d), 129.4 (d), 126.5 (2d),
124.1 (d), 115.7 (d), 62.0 (s, C-3), 38.1 (q, CH3N+), 20.6
(q, CH3), 17.5 (q, CH3).

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
6427
4.3.7. 3-Ethyl-2,3-dihydro-1,3-dimethyl-2-methylene-
1H-indole (2).2c Compound 45 (9.48 g, 30.1 mmol) in anhy-
drous ethanol (150 ml) was treated with KOH (3.38 g,
60.2 mmol). The solution was stirred for 3 h at room temper-
ature. After removal of the solvent, water was added and the
aqueous solution was extracted four times with diethyl ether.
The combined organic phases were dried over anhydrous
Na2SO4 and after evaporation of the solvent compound 2
4.4.4. 2,3-Dihydro-1,3,3-trimethyl-2-[(3-nitro-3-phenyl)-
propenylidene]-1H-indole (16). After 6 days, compound
16 was obtained in 45% yield. Reddish solid; mp 188–
190 ꢀC, IR (cmꢂ1, Nujol) 1616, 1568, 1489; UV (nm,
CH3OH) (log 3) 208 (4.29), 275 (4.12), 490 (4.42); UV
(nm, CH3CN) (log 3) 193 (4.76), 277 (4.05), 485 (4.46);
UV (nm, cyclohexane) (log 3) 195 (4.65), 251 (3.71), 279
1
(4.09), 434 (3.93), 450 (3.94); H NMR (d, ppm, CDCl3)
1
was obtained as a yellowish oil in 92% yield. H NMR
8.74 (1H, d, H-20, J¼13.5 Hz), 7.50–7.36 (5H, m, Ph),
7.27–7.22 (2H, m, H-6 and H-4) 7.04 (1H, t, H-5,
J¼7.4 Hz), 6.77 (1H, d, H-7, J¼8.2 Hz), 5.23 (1H, d, H-10,
J¼13.5 Hz), 3.09 (3H, s, CH3N), 1.71 (6H, s, gem-CH3).
13C NMR (d, ppm, CDCl3) 168.6 (s, C-2), 143.5 (s, C-7a),
139.6 (s), 139.5 (s), 135.5 (d, C-20), 131.4 (s), 130.9 (2d,
Ph), 128.4 (2d, Ph), 128.1 (d), 122.4 (d), 121.9 (d), 107.8
(d, C-7), 90.8 (d, C-10), 47.4 (s, C-3), 29.5 (q, CH3N), 28.7
and 13C NMR spectra were reported in the literature.2c IR
(cmꢂ1, film) 1649, 1608, 1492, 1462; EIMS (m/z) 187 (M+,
64), 158 (100); HRGC (OV1701) tR¼15.17 (10 min at
100 ꢀC, 3 ꢀC/min up to 200 ꢀC).
4.3.8. 2,3-Dihydro-1,3-dimethyl-2-methylene-3-phenyl-
1H-indole (3).38 2-Methyleneindoline 3 was obtained as an
orange oil in 92% yield by the same procedure described
for the synthesis of 2. IR (cmꢂ1, film) 1650, 1606, 1495,
ꢃ
(2q, CH3C); EIMS (m/z) 320 (M+ , 100); HRMS calcd for
C20H20N2O2 320.1525, found 320.1522.
1
1460; H NMR (d, ppm, CDCl3) 7.29–7.17 (5H, m, Ar-H),
4.4.5. (10E,20E)-3-Ethyl-2,3-dihydro-1,3-dimethyl-2-[(30-
nitro)propenylidene]-1H-indole (17). After 15 days, com-
pound 17 was obtained in 38% yield. Orange-brown solid;
mp 110–113 ꢀC. IR (cmꢂ1, Nujol) 1618, 1579, 1491; UV
(nm, CH3OH) (log 3) 209 (3.97), 277 (3.90), 483 (4.41);
UV (nm, CH3CN) (log 3) 195 (4.60), 280 (4.13), 477 (4.59);
UV (nm, cyclohexane) (log 3) 212 (4.01), 247 (3.68), 276
7.15 (1H, t, H-6, J¼7.3 Hz), 6.91 (1H, d, H-4, J¼7.3 Hz),
6.71 (1H, t, H-5, J¼7.3 Hz), 6.61 (1H, d, H-7, J¼7.7 Hz),
3.93 (1H, d, H-10, J¼1.8 Hz), 3.73 (1H, d, H-10, J¼1.8 Hz),
3.09 (3H, s, CH3N), 1.74 (3H, s, CH3C); 13C NMR (d,
ppm, CDCl3) 162.5 (s, C-2), 146.7 (s), 146.6 (s), 137.5 (s),
128.1 (d), 127.7 (d), 126.4 (d), 126.1 (d), 123.3 (d), 118.7
(d), 105.1 (d, C-7), 76.2 (d, C-10), 52.0 (s, C-3), 28.8 (q,
CH3), 28.0 (q, CH3).
1
(3.94), 420 (4.22), 440 (4.26); H NMR (d, ppm, CDCl3)
8.34 (1H, t, H-20, J¼13.1 Hz), 7.25 (2H, m, H-6 and H-4),
7.08 (1H, d, H-30, J¼12.1 Hz), 7.06 (1H, t, H-5, J¼7.5 Hz),
6.83 (1H, d, H-7, J¼8.05 Hz), 5.51 (1H, d, H-10,
J¼13.1 Hz), 3.30 (3H, s, CH3N), 1.92 (1H, m, HCHCH3),
1.80 (1H, m, HCHCH3), 1.30 (3H, s, CH3C), 0.47 (3H, t,
CH3CH2, J¼7.3 Hz). 13C NMR (d, ppm, CDCl3) 167.8 (s,
C-2), 144.4 (s, C-7a), 138.3 (d, C-20), 137.4 (s, C-3a),
129.1 (d), 128.1 (d), 122.5 (d), 121.9 (d), 107.7 (d, C-7),
90.1 (d, C-10), 52.5 (s, C-3), 35.0 (t, CH2CH3), 29.6 (q),
4.4. Nitroalkenylation reactions
4.4.1. General procedure. To a solution of the nitro-
enamines 4–6 (0.29 mmol) in CH2Cl2 (1.8 ml), a solution
of 2-methyleneindolines 1–3 (0.58 mmol) in CH2Cl2
(0.9 ml) and CeCl3$7H2O (0.108 g, 0.29 mmol) was added.
The reaction mixture was stirred at room temperature moni-
toring the course of the reaction by 1H NMR. At the end of the
reaction, water was added, and the organic phase was dried
over anhydrous Na2SO4. After evaporation of the solvent
the crude reaction mixture was purified by flash chromato-
graphy (light petroleum–ethyl acetate, 85:15) and products
14–22 were isolated.
ꢃ
28.1 (q), 8.8 (q, CH3CH2); EIMS (m/z) 258 (M+ , 100);
HRMS calcd for C15H18N2O2 258.1368, found 258.1363.
4.4.6. (10E,20E)-3-Ethyl-2,3-dihydro-1,3-dimethyl-2-[(30-
nitro)but-2-enylidene]-1H-indole (18). After 4 days com-
pound 18 was obtained in 42% yield. Purple solid; mp
168–169 ꢀC. IR (cmꢂ1, Nujol) 1620, 1595, 1572, 1489;
UV (nm, CH3OH) (log 3) 209 (4.01), 283 (3.99), 490
(4.48); UV (nm, CH3CN) (log 3) 192 (4.94), 280 (4.35),
480 (4.65); UV (nm, cyclohexane) (log 3) 216 (4.15), 248
4.4.2. 2,3-Dihydro-1,3,3-trimethyl-2-[(3-nitro) propenyl-
idene]-1H-indole (14). After 14 days, compound 14 was ob-
tained in 56% yield. All spectroscopic data are in accordance
1
(4.06), 280 (4.20), 428 (4.51), 448 (4.53); H NMR (d,
1
with those reported in the literature.16 Mp 161–162 ꢀC. H
ppm, CDCl3) 8.46 (1H, d, H-20, J¼13.5 Hz), 7.26 (1H, t,
H-6, J¼7.7 Hz), 7.20 (1H, d, H-4, J¼7.3 Hz), 7.04 (1H, t,
H-5, J¼7.3 Hz), 6.81 (1H, d, H-7, J¼8.0 Hz), 5.34 (1H, d,
H-10, J¼13.5 Hz), 3.31 (3H, s, CH3N), 2.26 (3H, s,
CH3CNO2), 2.22 (1H, m, HCHCH3), 2.05 (1H, m,
HCHCH3), 1.64 (3H, s, CH3C), 0.47 (3H, t, CH3CH2,
J¼7.3 Hz). 13C NMR (d, ppm, CDCl3) 165.9 (s, C-2),
144.6 (s, C-7a), 137.3 (s), 136.0 (s), 133.3 (d, C-20), 128.0
(d, C-6), 122.1 (d, Ar), 121.9 (d, Ar), 107.3 (d, C-7), 90.8
(d, C-10), 52.2 (s, C-3), 34.9 (t, CH2CH3), 29.5 (q), 28.1
NMR (d, ppm, CDCl3) 8.38 (1H, dd, H-20, J1¼13.2 Hz,
J1¼12.1 Hz), 7.27 (2H, t+d, H-6 and H-4), 7.10 (1H, d, H-
30, J¼12.1 Hz), 7.06 (1H, t, H-5), 6.85 (1H, d, H-7), 5.46
(1H, d, N–C]CH, J¼13.2 Hz), 3.30 (3H, s, NCH3), 1.64
(6H, s, gem-CH3).
4.4.3. 2,3-Dihydro-1,3,3-trimethyl-2-[(3-nitro) but-2-enyl-
idene]-1H-indole (15). After 14 days, compound 15 was
obtained as a purple solid in 53% yield. All spectroscopic
data are in accordance with those reported in the literature.16
ꢃ
(q), 12.0 (q, C-40), 8.9 (q, CH3CH2); EIMS (m/z) 272 (M+ ,
1
Mp 191–192 ꢀC. H NMR (d, ppm, CDCl3) 8.50 (1H, d,
100); HRMS calcd for C16H20N2O2 272.1525, found
272.1520.
H-20, J¼13.2 Hz), 7.27 (1H, t, H-6), 7.24 (1H, d, H-4),
7.03 (1H, t, H-5), 6.84 (1H, d, H-7), 5.30 (1H, d, H-10,
J¼13.2 Hz), 3.32 (3H, s, NCH3), 2.25 (3H, s, CH3), 1.64
(6H, s, gem-CH3).
4.4.7. (10E,20E)-3-Ethyl-2,3-dihydro-1,3-dimethyl-2-[(30-
nitro-30-phenyl)propenylidene]-1H-indole (19). After 7

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O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
days compound 19 was obtained in 44% yield. Red solid;
mp 126–128 ꢀC. IR (cmꢂ1, Nujol) 1616, 1586, 1570, 1491;
UV (nm, CH3OH) (log 3) 208 (4.25), 284 (3.95), 491
(4.57); UV (nm, CH3CN) (log 3) 193 (3.91), 276 (4.16),
488 (4.56); UV (nm, cyclohexane) (log 3) 195 (4.68), 279
487 (4.35); UV (nm, CH3CN) (log 3) 193 (4.98), 260
(4.17), 484 (4.40); UV (nm, cyclohexane) (log 3) 210
(4.49), 254 (3.98), 429 (4.15), 443 (4.13); H NMR (d,
1
ppm, CDCl3) 8.07 (1H, d, H-20, J¼13.2 Hz), 7.66–6.82
(14H, m), 5.20 (1H, d, H-10, J¼13.2 Hz), 3.20 (3H, s,
CH3N), 1.99 (3H, s, CH3C). 13C NMR (d, ppm, CDCl3)
168.4 (s, C-2), 143.6 (s), 143.0 (s), 140.1 (s), 135.6 (d, C-
20), 131.4 (s), 130.9 (2d), 129.0 (2d), 128.4 (d), 128.3 (2d),
128.1 (d), 127.4 (d), 126.1 (2d), 123.2 (d), 122.5 (d), 107.7
(d, C-7), 90.4 (d, C-10), 54.5 (s, C-3), 29.6 (q), 27.1 (q); an
aromatic singlet was hidden under other signals; EIMS
1
(4.21), 436 (4.45), 452 (4.46); H NMR (d, ppm, CDCl3)
8.71 (1H, d, H-20, J¼13.5 Hz), 7.60–7.40 (6H, m, Ph and
H-6), 7.23 (1H, m, H-4), 7.04 (1H, t, H-5, J¼7.3 Hz), 6.77
(1H, d, H-7, J¼7.9 Hz), 5.30 (1H, d, H-10, J¼13.5 Hz),
3.09 (3H, s, CH3N), 2.31 (1H, m, HCHCH3), 2.09 (1H, m,
HCHCH3), 1.69 (3H, s, CH3C), 0.49 (3H, t, CH3CH2,
J¼7.3 Hz). 13C NMR (d, ppm, CDCl3) 167.0 (s, C-2),
144.5 (s, C-7a), 139.3 (s), 137.5 (s), 135.2 (d, C-20), 131.5
(s), 131.0 (2d), 128.4 (2d), 128.1 (d), 122.4 (d), 121.9 (d),
107.6 (d, C-7), 91.3 (d, C-10), 52.5 (s, C-3), 35.1 (t,
CH2CH3), 29.5 (q), 28.2 (q), 9.0 (q, CH3CH2); EIMS (m/z)
ꢃ
(m/z) 382 (M+ , 75), 335 (54), 334 (24), 320 (20), 273
(23), 262 (53), 258 (16), 247 (56), 246 (40), 244 (27), 232
(47), 231 (31), 230 (23), 221 (100); HRMS calcd for
C25H22N2O2 382.1681, found 382.1686.
ꢃ
334 (M+ , 53), 273 (31), 260 (100); HRMS calcd for
4.4.11. (10E,20E)-2,3-Dihydro-2-[(30-(2-methylthio-
phenyl)-30-nitro)propenylidene]-1,3,3-trimethyl-1H-
indole (23). To a solution of the nitroenamine 7 (0.038 g,
0.14 mmol) and 2-methyleneindoline 1 (0.05 g, 0.29 mmol)
in CH2Cl2 (2 ml), Zn(OTf)2 (0.105 g, 0.29 mmol) was added.
The reaction mixture was stirred at room temperature. After
12 days water was added, and the organic phase was dried
over Na2SO4 anhydrous. After evaporation of the solvent
the crude reaction mixture was purified by flash chromato-
graphy (light petroleum–ethyl acetate, 85:15) to give com-
pound 23 (0.015 g, 30% yield). Red oil; IR (cmꢂ1, Nujol)
1580; UV (nm, CH3OH) (log 3) 209 (4.50), 254 (4.08), 281
(3.97), 489 (4.42); UV (nm, CH3CN) (log 3) 203 (4.46),
209 (4.47), 259 (4.10), 288 (3.99), 489 (4.48); UV (nm, cy-
clohexane) (log 3) 201 (4.24), 210 (4.41), 259 (4.09), 281
C21H22N2O2 334.1681, found 334.1680.
4.4.8. (10E,20E)-2,3-Dihydro-1,3-dimethyl-2-[(30-nitro)-
propenylidene]-3-phenyl-1H-indole (20). After 8 days
compound 20 was obtained in 31% yield. Red solid; mp
152–159 ꢀC. IR (cmꢂ1, film) 1620, 1574, 1491; UV (nm,
CH3OH) (log 3) 208 (4.41), 275 (3.94), 477 (4.15); UV
(nm, CH3CN) (log 3) 194 (5.02), 277 (4.24), 473 (4.55);
UV (nm, cyclohexane) (log 3) 197 (4.66), 271 (4.11), 417
1
(4.43), 434 (4.45); H NMR (d, ppm, CDCl3) 7.70 (1H, t,
H-20, J¼12.9 Hz), 7.46–7.22 (6H, m), 6.94–6.88 (4H, m),
5.41 (1H, d, H-10, J¼12.9 Hz), 3.40 (3H, s, CH3N), 1.93
(3H, s, CH3C). 13C NMR (d, ppm, CDCl3) 169.2 (s, C-2),
143.5 (s), 142.8 (s), 140.0 (s), 138.7 (d), 129.9 (d), 129.0
(2d), 128.1 (d), 127.4 (d), 126.0 (2d), 123.2 (d), 122.6 (d),
107.9 (d, C-7), 89.3 (d, C-10), 54.5 (s, C-3), 29.7 (q), 27.1
1
(3.99), 432 (4.35), 451 (4.36); H NMR (d, ppm, CDCl3),
8.74 (1H, d, H-20, J¼13.5 Hz), 7.45–7.15 (6H, m), 7.04,
(1H, t, J¼7.7 Hz), 6.77 (1H, d, H-7, J¼8.0 Hz), 4.93 (1H,
d, H-10, J¼13.5 Hz), 3.06 (3H, s, CH3N), 2.42 (3H, s,
ꢃ
(q); EIMS (m/z) 306 (M+ , 25), 259 (49), 244 (13), 237
(70), 235 (30), 234 (22), 222 (100); HRMS calcd for
C19H18N2O2 306.1368, found 306.1365.
CH3S), 1.72 (3H, s, gem-CH3), 1.70 (3H, s, gem-CH3); 13
C
NMR (d, ppm, CDCl3) 168.8 (s, C-2), 143.5 (s), 140.4 (s),
139.6 (s), 138.0 (s), 136.6 (d), 131.7 (d), 130.3 (s), 129.6
(d), 128.0 (d), 126.0 (d), 125.1 (d), 122.4 (d), 121.8 (d),
107.8 (d, C-7), 90.7 (d, C-10), 47.5 (s, C-3), 29.6 (q,
CH3N), 28.8 (q, gem-CH3), 28.7 (q, gem-CH3), 15.8 (q,
4.4.9. (10E,20E)-2,3-Dihydro-1,3-dimethyl-3-phenyl-2-
[(30-nitro)but-2-enylidene]-1H-indole (21). After 4 days
compound 21 was obtained in 42% yield. Red solid; mp
174–176 ꢀC. IR (cmꢂ1, Nujol) 1616, 1597, 1574, 1487; UV
(nm, CH3OH) (log 3) 207 (4.29), 276 (4.28), 483 (4.46);
UV (nm, CH3CN) (log 3) 194 (4.72), 280 (4.07), 477
(4.49); UV (nm, cyclohexane) (log 3) 210 (4.21), 248
ꢃ
SCH3); EIMS (m/z) 366 (M+ , 100); HRMS calcd for
C21H22N2O2S 366.1402, found 366.1405.
1
(3.77), 421 (3.86), 440 (3.85); H NMR (d, ppm, CDCl3)
4.5. Nitroalkylation reactions
7.82 (1H, d, H-20, J¼13.0 Hz), 7.33–7.20 (5H, m), 6.92–
6.86 (4H, m), 5.25 (1H, d, H-10, J¼13.0 Hz), 3.40 (3H, s,
CH3N), 2.12 (3H, s, CH3CNO2), 1.93 (3H, s, CH3C). 13C
NMR (d, ppm, CDCl3) 167.4 (s, C-2), 143.7 (s), 143.0 (s),
139.9 (s), 136.7 (s), 133.6 (d, C-20), 128.8 (2d), 128.0 (d),
127.2 (d), 126.1 (2d), 123.2 (d), 122.2 (d), 107.5 (d, C-7),
89.9 (d, C-10), 54.3 (s, C-3), 29.7 (q), 26.9 (q), 12.0 (q);
4.5.1. General procedure. To a solution of 2-methylenindo-
lines 1–3 (3 mmol) in diethyl ether (7 ml), a solution of
nitroolefins 8–10 (3 mmol) in diethyl ether (3.5 ml) was
added at ꢂ15/ꢂ5 ꢀC. The solution was allowed to warm
to room temperature and the course of the reaction was
1
monitored by H NMR. After 2–3 days the products ob-
tained 24–32 were purified by flash chromatography (light
petroleum–ethyl acetate, 95:5).
ꢃ
EIMS (m/z) 320 (M+ , 88), 303 (15), 289 (14), 273 (56),
272 (20), 258 (41), 243 (22), 241 (16), 237 (29), 234 (33),
231 (16), 221 (100); HRMS calcd for C20H20N2O2
320.1525, found 320.1523.
4.5.2. (E)-2,3-Dihydro-1,3,3-trimethyl-2-[(2-methyl-3-
nitro)propylidene]-1H-indole (24). 62% Yield; yellow oil;
IR (cmꢂ1, film) 1658, 1604, 1547, 1496, 1454; UV (nm,
CH3OH) (log 3) 210 (4.29), 280 (4.13); UV (nm, CH3CN)
(log 3) 195 (4.58), 204 (4.54), 282 (4.26); UV (nm, cyclohex-
4.4.10. (10E,20E)-2,3-Dihydro-1,3-dimethyl-3-phenyl-2-
[(30-nitro-30-phenyl)propenylidene]-1H-indole (22).
After 15 days compound 22 was obtained in 26% yield.
Red solid; mp 179–180 ꢀC. IR (cmꢂ1, Nujol) 1618, 1572,
1491; UV (nm, CH3OH) (log 3) 209 (4.60), 263 (4.12),
1
ane) (log 3) 194 (4.73), 207 (4.61), 281 (4.42); H NMR (d,
ppm, CDCl3) 7.10 (1H, t, H-6, J¼7.7 Hz), 7.04 (1H, d, H-4,

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
6429
J¼7.0 Hz), 6.73 (1H, t, H-5, J¼7.3 Hz), 6.47 (1H, d, H-7,
J¼7.7 Hz), 4.30 (2H, m, CH2NO2), 3.96 (1H, d, H-10, J¼
11.0 Hz), 3.61 (1H, m, H-20), 2.95 (3H, s, CH3N), 1.50 (3H,
s, CH3C), 1.49 (3H, s, CH3C), 1.17 (3H, d, CH3CH,
J¼6.6 Hz); 13C NMR (d, ppm, CDCl3) 155.0 (s, C-2), 145.5
(s, C-7a), 137.4 (s, C-3a), 127.4 (d, C-6), 121.0 (d, C-4),
118.0 (d, C-5), 104.5 (d, C-7), 93.5 (d, C-10), 82.3 (t, C-30),
44.2 (s, C-3), 31.2 (d, C-20), 28.5 (q, CH3N), 28.0 (q,
CH3C), 27.8 (q, CH3C), 20.3 (q, CH3CH); EIMS (m/z) 260
4.5.5. (E)-3-Ethyl-2,3-dihydro-1,3-dimethyl-2-[(2-methyl-
3-nitro)propylidene]-1H-indole (27a,b). The isomers 27a
and 27b (80% yield) were obtained in 9:1 ratio (determined
by HRGC) and were not separable by flash chromatography.
Yellow oil; IR (cmꢂ1, film) 1655, 1606, 1551, 1496, 1460;
UV (nm, CH3OH) (log 3) 211 (4.34), 282 (4.37); UV (nm,
CH3CN) (log 3) 192 (4.53), 204 (4.46), 282 (4.30). UV
(nm, cyclohexane) (log 3) 216 (4.00), 280 (4.30); EIMS (m/
ꢃ
z) 274 (M+ , 56), 245 (13), 228 (21), 214 (40), 198 (80),
ꢃ
(M+ , 90), 230 (13), 214 (15), 200 (35), 198 (15), 185 (24),
184 (33), 183 (21), 182 (16), 174 (100); HRMS calcd for
C16H22N2O2 274.1681, found 274.1683; HRGC (OV1701)
tR¼45.00 min for 27b; tR¼45.44 min for 27a (10 min at
100 ꢀC, 3 ꢀC/min up to 200 ꢀC). For clarity sake the NMR
values are given separately for each isomer. Compound
27a: 1H NMR (d, ppm, CDCl3) 7.10 (1H, t, H-6,
J¼7.5 Hz), 6.99 (1H, d, H-4, J¼7.3 Hz), 6.73 (1H, t, H-5,
J¼7.3 Hz), 6.46 (1H, d, H-7, J¼7.5 Hz), 4.30 (2H, m,
CH2NO2), 4.02 (1H, d, H-10, J¼11.0 Hz), 3.57 (1H, m, H-
20), 2.94 (3H, s, CH3N), 1.92 (1H, m, HCHCH3), 1.80 (1H,
m, HCHCH3), 1.50 (3H, s, CH3C), 1.16 (3H, d, CH3CH,
J¼6.6 Hz), 0.56 (3H, t, CH3CH2, J¼7.3 Hz); 13C NMR (d,
ppm, CDCl3) 152.9 (s, C-2), 146.7 (s, C-7a), 135.3 (s, C-
3a), 127.5 (d, C-6), 121.3 (d, C-4), 118.1 (d, C-5), 104.4 (d,
C-7), 93.8 (d, C-10), 82.7 (t, CH2NO2), 49.4 (s, C-3), 33.8
(t, CH2CH3), 31.2 (d, C-20), 28.8 (q, CH3N), 27.4 (q,
CH3C), 20.4 (q, CH3CH), 9.3 (q, CH3CH2). Compound
27b: 1H NMR (d, ppm, CDCl3) 6.78 (1H, t, H-5,
J¼7.7 Hz), 6.54 (1H, d, H-7, J¼7.7 Hz), 4.03 (1H, d, H-10,
J¼10.6 Hz), 1.16 (3H, d, CH3CH, J¼6.2 Hz), 0.44 (3H, t,
CH3CH2, J¼7.3 Hz); 13C NMR (d, ppm, CDCl3) 153.4 (s,
C-2), 148.2 (s, C-7a), 121.9 (d, C-4), 118.8 (d, C-5), 105.2
(d, C-7), 94.0 (d, C-10), 82.5 (t, CH2NO2), 34.0 (t,
CH2CH3), 31.4 (d, C-20), 20.8 (q, CH3CH), 8.7 (q, CH3CH2).
184 (22), 175 (50), 160 (100); HRMS calcd for
C15H20N2O2 260.1525, found 260.1524.
4.5.3. (E) and (Z)-2,3-Dihydro-1,3,3-trimethyl-2-[(3-
nitro-2-phenyl)propylidene]-1H-indole (25a,b). The two
compounds (E)-25a and (Z)-25b in ratio 9:1, respectively,
were inseparable by flash chromatography. 75% Yield; yel-
low oil; IR (cmꢂ1, film) 1653, 1604, 1550, 1491, 1456; UV
(nm, CH3OH) (log 3) 210 (4.48), 283 (4.47); UV (nm,
CH3CN) (log 3) 193 (5.02), 206 (4.62), 285 (4.54). UV
(nm, cyclohexane) (log 3) 197 (4.42), 210 (4.50), 284
ꢃ
(4.38). EIMS (m/z) 322 (M+ , 22), 276 (16), 262 (100);
HRMS calcd for C20H22N2O2 322.1681, found 322.1682.
For clarity sake the NMR values are given separately for
each isomer. Compound (E)-25a: 1H NMR (d, ppm,
CDCl3) 7.41 (5H, m, Ph), 7.09 (1H, t, H-6, J¼7.7 Hz), 7.03
(1H, d, H-4, J¼7.0 Hz), 6.73 (1H, t, H-5, J¼7.3 Hz), 6.47
(1H, d, H-7, J¼8.1 Hz), 4.77 (1H, m, CHPh), 4.68 (1H, dd,
CHNO2, J1¼7.7 Hz, J2¼11.2 Hz), 4.51 (1H, dd, CHNO2,
J1¼7.8 Hz, J2¼11.2 Hz), 4.39 (1H, d, H-10, J¼10.6 Hz),
3.00 (3H, s, CH3N), 1.59 (3H, s, CH3C), 1.41 (3H, s,
CH3C). 13C NMR (d, ppm, CDCl3) 156.2 (s, C-2), 145.8
(s), 141.8 (s), 138.0 (s), 129.2 (2d), 127.7 (d, C-6), 127.4
(d), 127.1 (2d), 121.4 (d, C-4), 118.5 (d, C-5), 105.0 (d, C-
7), 90.8 (d, C-10), 82.3 (t, C-30), 44.7 (s, C-3), 41.7 (d,
CHPh), 29.2 (q, CH3N), 28.3 (q, CH3C), 28.1 (q, CH3C).
4.5.6. (E)-3-Ethyl-2,3-dihydro-1,3-dimethyl-2-[(3-nitro-
2-phenyl)propylidene]-1H-indole (28a,b). The isomers
28a and 28b (94% yield) were obtained in 3:2 ratio and
were not separable by flash chromatography. Yellow solid;
mp 73–81 ꢀC; IR (cmꢂ1, Nujol) 1650, 1605, 1550, 1495;
UV (nm, CH3OH) (log 3) 211 (4.48), 285 (4.48); UV (nm,
CH3CN) (log 3) 192 (4.96), 208 (4.60), 288 (4.50). UV
(nm, cyclohexane) (log 3) 216 (4.27), 284 (4.57); EIMS
1
Compound (Z)-25b, only a few signals were identified. H
NMR (d, ppm, CDCl3) 6.56 (1H, d, H-7), 4.98 (1H, m,
CHPh), 4.65 (1H, dd, CHNO2, J1¼6.2 Hz, J2¼11.3 Hz),
4.50 (1H, m, CHNO2), 4.25 (1H, d, H-10, J¼9.9 Hz), 3.32
(3H, s, CH3N), 1.31 (3H, s, CH3), 1.30 (3H, s, CH3); 13C
NMR (d, ppm, CDCl3) 121.8 (d, C-4), 119.2 (d, C-5),
105.5 (d, C-7), 88.6 (d, C-10), 41.2 (d, CHPh) 33.0 (q, CH3N).
ꢃ
(m/z) 336 (M+ , 33), 276 (45), 260 (26), 247 (31), 246 (17),
232 (13), 202 (48), 174 (100); HRMS calcd for
C21H24N2O2 336.1838, found 336.1833. For clarity sake
the NMR values are given separately for each isomer.
4.5.4. (E)-2,3-Dihydro-1,3,3-trimethyl-2-[(2-nitrocyclo-
hexyl)methylidene]-1H-indole (26a,b). Compounds 26a,b
1
1
were reported in the literature.16 Compound 26a. H NMR
Compound 28a: H NMR (d, ppm, CDCl3) 7.33 (5H, m,
(d, ppm, CDCl3) 7.08 (1H, t, H-6), 7.01 (1H, d, H-4), 6.71
(1H, t, H-5), 6.45 (1H, d, H-7), 4.76 (1H, dt, CHNO2, J1¼
J2¼4.8 Hz, J3¼9.5 Hz, WH¼16.5 Hz), 4.34 (1H, d, H-10,
J¼11.4 Hz), 3.51 (1H, m, CHCHNO2, WH¼21.5 Hz), 2.95
(3H, s, NCH3), 2.26 (1H, m, annular H), 2.0 (3H, m, annular
H), 1.78 (1H, m, annular H), 1.45 (3H, s, CH3 at C-3), 1.41
(3H, s, CH3 at C-3), 1.40 (1H, m, annular H), 1.20 (1H, m, an-
Ph), 7.09 (1H, t, H-6, J¼7.7 Hz), 6.98 (1H, d, H-4,
J¼7.0 Hz), 6.73 (1H, t, H-5, J¼7.3 Hz), 6.46 (1H, d, H-7,
J¼8.0 Hz), 4.74–4.61 (2H, m, CHPh+CHNO2), 4.54–4.46
(2H, m, CHNO2+H-10), 3.00 (3H, s, CH3N), 1.92 (1H, m,
HCHCH3), 1.80 (1H, m, HCHCH3), 1.58 (3H, s, CH3C),
0.25 (3H, t, CH3CH2, J¼7.3 Hz); 13C NMR (d, ppm,
CDCl3) 153.8 (s, C-2), 146.6 (s), 141.1 (s), 135.4 (s), 128.9
(d), 127.6 (d, C-6), 127.1 (3d, Ph), 121.3 (d, C-4), 118.4 (d,
C-5), 104.6 (d, C-7), 91.1 (d, C-10), 82.3 (t, C-30), 49.6 (s,
C-3), 41.5 (d, CHPh), 33.9 (t, CH2CH3), 28.9 (q, CH3N),
27.5 (q, CH3C), 8.9 (q, CH3CH2). Compound 28b: 1H
NMR (d, ppm, CDCl3) 6.78 (1H, t, H-5, J¼7.3 Hz), 6.52
(1H, d, H-7, J¼8.0 Hz), 3.01 (3H, s, CH3N), 1.38 (3H, s,
CH3C), 0.55 (3H, t, CH3CH2, J¼7.3 Hz). 13C NMR (d,
ppm, CDCl3) 153.9 (s, C-2), 141.4 (s, C-3a), 91.0 (d, C-10),
49.6 (s, C-3), 9.3 (q, CH3CH2).
1
nular H). Compound 26b. H NMR (d, ppm, CDCl3) 7.07
(1H, t, H-6), 7.01 (1H, d, H-4), 6.70 (1H, t, H-5), 6.43 (1H,
d, H-7), 4.25 (1H, ddd, CHNO2, J1¼11.7 Hz, J2¼10.6 Hz,
J3¼3.7 Hz, WH¼27.5 Hz), 4.05 (1H, d, H-10, J¼10.6 Hz),
3.05 (1H, dq, CHCHNO2, J1¼J2¼J3¼10.6 Hz, J4¼
10.6 Hz, J3¼3.7 Hz), 2.92 (3H, s, NCH3), 2.26 (1H, m, annu-
lar H), 2.01 (1H, dq, annular H), 1.96 (3H, m, annular H), 1.76
(2H, m, annular H), 1.50 (1H, m, annular H), 1.46 (4H, s+m,
CH3 at C-3, annular H), 1.42 (3H, s, CH3 at C-3).

6430
O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
4.5.7. (E)-3-Ethyl-2,3-dihydro-1,3-dimethyl-2-[(2-nitro-
cyclohexyl)methylidene]-1H-indole (29a,b). In the crude
reaction mixture the isomers cis-29a and trans-29b were de-
tected in 3:1 ratio. After purification on flash chromato-
graphy fractions of different composition were obtained
(45% yield). Yellow solid; mp 110–115 ꢀC (for 1:9 ratio of
cis-29a and trans-29b, respectively); IR (cmꢂ1, Nujol)
1658, 1606, 1550, 1496; UV (nm, CH3OH) (log 3) 210
(4.39), 282 (4.41); UV (nm, CH3CN) (log 3) 192 (4.82),
204 (4.55), 284 (4.48); UV (nm, cyclohexane) (log 3) 216
only some signals were identified. 1H NMR (d, ppm,
CDCl3) 3.95 (1H, d, H-10, J¼10.6 Hz), 3.64 (1H, dd,
CHNO2, J1¼9.1 Hz, J2¼11.3 Hz), 3.36 (1H, dd, CHNO2,
J1¼4.6 Hz, J2¼11.6 Hz), 3.24 (3H, s, CH3N), 1.79 (3H, s,
CH3C), 1.04 (3H, d, CH3CH, J¼6.6 Hz); 13C NMR (d,
ppm, CDCl3) 156.4 (s, C-2), 145.6 (s), 145.5 (s), 138.3 (s),
134.8 (s), 128.5 (d), 128.4 (d), 128.2 (d), 128.1 (d), 127.7
(d), 127.2 (d), 126.6 (d), 126.3 (d), 122.8 (d), 122.7 (d), for
30a: 118.6 (d, C-5), 104.9 (d, C-7), 94.0 (d, C-10), 82.6
(t, C-30), 51.9 (s, C-3), 31.7 (d, C-20), 29.0 (q, CH3N), 25.9
(q, CH3C), 18.7 (q, CH3CH); for 30b: 118.7 (d, C-5), 105.0
(d, C-7), 93.5 (d, C-10), 80.6 (t, C-30), 52.1 (s, C-3), 30.6
(d, C-20), 26.5 (q), 25.4 (q), 23.7 (q).
ꢃ
(4.20), 284 (4.51). EIMS (m/z) 314 (M+ , 100); HRMS calcd
for C19H26N2O2 314.1994, found 314.1995. For clarity sake
the NMR values are given separately for each isomer.
Compound 29a: H NMR (d, ppm, CDCl3) 7.07 (1H, t,
1
H-6, J¼7.7 Hz), 6.94 (1H, d, H-4, J¼6.2 Hz), 6.70 (1H, t,
H-5, J¼7.1 Hz), 6.43 (1H, d, H-7, J¼7.7 Hz), 4.62 (1H, dt,
CHNO2, J1¼J2¼4.3 Hz, J3¼8.8 Hz, WH¼16 Hz), 4.39
(1H, d, H-10, J¼11.0 Hz), 3.42 (1H, m, CHCHNO2,
WH¼24 Hz), 2.93 (3H, s, CH3N), 2.23 (1H,m), 1.86 (3H,
m), 1.78 (2H, m, CH2CH3), 1.65 (2H, m), 1.45 (2H, m),
1.40 (3H, s, CH3C), 0.53 (3H, t, CH3CH2, J¼7.1 Hz). 13C
NMR (d, ppm, CDCl3) 153.1 (s, C-2), 146.7 (s, C-7a),
135.4 (s, C-3a), 127.5 (d, C-6), 121.2 (d, C-4), 117.9 (d,
C-5), 104.3 (d, C-7), 89.6 (d, C-10), 87.6 (d, CHNO2), 49.3
(s, C-3), 35.8 (d, CHCHNO2), 34.0 (t, CH2CH3), 31.8 (t,
CH2), 28.9 (q, CH3N), 27.8 (q, CH3C), 26.0 (t, CH2), 22.5
(t, CH2), 21.3 (t, CH2), 9.4 (q, CH3CH2). Compound 29b:
1H NMR (d, ppm, CDCl3) 7.06 (1H, t, H-6, J¼7.1 Hz),
6.93 (1H, d, H-4, J¼7.3 Hz), 6.68 (1H, t, H-5, J¼7.3 Hz),
6.41 (1H, d, H-7, J¼8.0 Hz), 4.22 (1H, m, CHNO2,
WH¼26 Hz), 4.09 (1H, d, H-10, J¼10.6 Hz), 3.01 (1H, dq,
CHCHNO2, J1¼J2¼J3¼10.8 Hz, J4¼3.8 Hz), 2.90 (3H, s,
CH3N), 2.23 (1H, m), 1.95 (1H, m), 1.87 (2H, m), 1.77
(2H, m, CH2CH3), 1.75 (1H, m), 1.42 (3H, s, CH3C), 1.35
(2H, m), 1.22 (1H, m), 0.53 (3H, t, CH3CH2, J¼7.3 Hz);
13C NMR (d, ppm, CDCl3) 152.9 (s, C-2), 146.7 (s, C-7a),
135.4 (s, C-3a), 127.4 (d, C-6), 121.2 (d, C-4), 117.9 (d,
C-5), 104.3 (d, C-7), 94.3 (d, C-10), 92.3 (d, CHNO2), 49.4
(s, C-3), 40.0 (d, CHCHNO2), 34.3 (t, CH2CH3), 34.2 (t,
CH2), 31.0 (t, CH2), 28.8 (q, CH3N), 27.7 (q, CH3C), 24.8
(t, CH2), 24.0 (t, CH2), 9.4 (q, CH3CH2).
4.5.9. (E)-2,3-Dihydro-1,3-dimethyl-2-[(3-nitro-2-phe-
nyl)propylidene]-3-phenyl-1H-indole (31a,b). The iso-
mers 31a and 31b (13% yield) inseparable by flash
chromatography, were obtained in 1:1 ratio. Orange oil; IR
(cmꢂ1, film) 1651, 1606, 1552, 1491, 1458; UV (nm,
CH3OH) (log 3) 209 (4.50), 285 (4.15); UV (nm, CH3CN)
(log 3) 193 (4.93), 206 (4.66), 286 (4.23); UV (nm, cyclohex-
ane) (log 3) 196 (4.69), 205 (4.63), 285 (4.32); EIMS (m/z)
ꢃ
384 (M+ , 31), 338 (18), 324 (91), 310 (32), 308 (19), 246
(13), 231 (22), 230 (18), 223 (100); HRMS calcd for
C25H24N2O2 384.1838, found 384.1838; 1H NMR (d, ppm,
CDCl3) 7.35–7.06 (10H, m, Ph), 6.70–6.40 (4H, m, Ar),
4.56 (0.5H, dd, CHNO2, J1¼7.10 Hz, J2¼11.2 Hz, for
31a), 4.48 (0.5H, m, CHNO2 for 31a), 4.40 and 4.36 (1H,
d, H-10, J¼11.0 Hz), 4.14 (0.5H, dd, CHNO2, J1¼8.8 Hz,
J2¼11.3 Hz, for 31b), 4.11 (1H, m, CHPh, for 31a and
31b), 3.60 (0.5H, dd, CHNO2, J1¼4.9 Hz, J2¼11.2 Hz, for
31b), 3.10 (3H, s, CH3N for 31a and 31b), 1.91 and 1.78
(3H, s, CH3C); 13C NMR (d, ppm, CDCl3) 156.9 and 156.7
(s, C-2), 144.9 (2s), 141.2 (s), 139.9 (s), 138.4 (2s), 128.8
(d), 128.6 (d), 128.4 (d), 128.3 (d), 127.8 (d), 127.7 (d),
127.1 (2d), 126.7 (2d), 126.6 (2d), 126.4 (d), 122.8 (2d) (d,
C-4), 119.0 and 118.9 (d, C-5), 105.1 and 105.2 (d, C-7),
91.7 and 91.3 (d, C-10), 81.7 and 79.9 (t, C-30), 52.2 and
52.1 (s, C-3), 42.1 and 41.0 (d, CHPh), 29.1 (2q, CH3N for
31a and 31b), 26.0 and 25.4 (q, CH3C).
4.5.10. 2,3-Dihydro-1,3-dimethyl-2-[(2-nitrocyclohexyl)
methylidene]-3-phenyl-1H-indole (32a,b,c). 1H NMR
analysis of the crude reaction mixture indicated the presence
of three isomers, cis-32a, trans-32b and cis-32c in 60%, 25%
and 15%, respectively. After purification on flash chromato-
graphy fractions of different composition in cis-32a, trans-
32b and trans-32d were isolated in only 6% yield. Oil; IR
(cmꢂ1, film) 1660, 1601, 1551, 1507; UV (nm, CH3OH)
(log 3) 211 (4.34), 280 (4.09); UV (nm, CH3CN) (log 3)
196 (4.36), 212 (4.22), 281 (4.01); UV (nm, cyclohexane)
(log 3) 201 (4.27), 212 (4.32), 279 (4.08); EIMS (m/z) 362
4.5.8. (E)-2,3-Dihydro-1,3-dimethyl-2-[(2-methyl-3-
nitro)propylidene]-3-phenyl-1H-indole (30a,b). The iso-
mers 30a and 30b (30% yield) inseparable by flash
chromatography, were obtained in 3:1 ratio, respectively (de-
termined by HRGC). Yellow oil; IR (cmꢂ1, film) 1650, 1600,
1550, 1495, 1460; UV (nm, CH3OH) (log 3) 208 (4.24), 276
(4.17); UV (nm, CH3CN) (log 3) 194 (4.73), 207 (4.56), 281
(4.07); UV (nm, cyclohexane) (log 3) 195 (4.62), 207 (4.52),
ꢃ
280 (4.18); EIMS (m/z) 322 (M+ , 12), 276 (15), 262 (37), 246
(15), 238 (52), 236 (23), 222 (100); HRMS calcd for
C20H22N2O2 322.1681, found 322.1680; HRGC (OV1701)
tR¼39.97 min for 30a, tR¼40.97 min for 30b (200 ꢀC iso-
therm). For clarity sake the 1H NMR values are given sepa-
ꢃ
(M+ , 28), 316 (10), 237 (15), 234 (14), 222 (100); HRMS
calcd for C23H26N2O2 362.1994, found 362.1990. For clarity
sake the NMR values are given separately for each isomer.
Compound cis-32c: H NMR (d, ppm, CDCl3) 7.28–7.16
1
1
rately for each isomer. Compound 30a: H NMR (d, ppm,
CDCl3) 7.32–7.23 (4H, m, Ph), 7.19–7.15 (1H, m, Ph),
7.08 (1H, t, H-6, J¼7.5 Hz), 6.71 (1H, d, H-4, J¼7.0 Hz),
6.62 (1H, t, H-5, J¼7.0 Hz), 6.55 (1H, d, H-7, J¼7.3 Hz),
4.19 (2H, AB part of an ABX system, CH2NO2,
JAB¼7.3 Hz), 3.99 (1H, d, H-10, J¼10.6 Hz), 3.07 (3H, s,
CH3N), 2.95 (1H, m, CHCH3, J¼7.0 Hz), 1.81 (3H, s,
CH3C), 0.50 (3H, d, CH3CH, J¼6.2 Hz). Compound 30b,
(5H, m, Ph), 7.08 (1H, t, Ar, J¼7.4 Hz), 6.67–6.53 (3H, m,
Ar), 4.48 (1H, dt, CHNO2, J1¼J2¼4.2 Hz, J3¼8.6 Hz,
WH¼18.4 Hz), 4.33 (1H, d, H-10, J¼11.2 Hz), 3.07 (3H, s,
CH3N), 2.78 (1H, m), 2.12 (1H, m), 1.9–0.5 (7H, m), 1.72
(3H, s, CH3C); 13C NMR (d, ppm, CDCl3) 156.6 (s, C-2),
146.3 (s), 145.8 (s), 138.6 (s), 128.1 (d), 127.5 (d), 126.8
(d), 126.2 (d), 122.7 (d, C-4), 118.4 (d, C-5), 104.9 (d,

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
6431
C-7), 89.9 (d, C-10), 87.7 (d, CHNO2), 51.8 (s, C-3), 36.3 (d,
CHCHNO2), 29.7 (t, CH2), 29.5 (t, CH2), 29.2 (q, CH3N),
26.4 (t, CH2), 26.2 (q, CH3C), 22.4 (t, CH2). Compound
trans-32b: 1H NMR (d, ppm, CDCl3) 4.10 (1H, dt,
CHNO2, J1¼J2 11.2 Hz, J3¼3.5 Hz, WH¼30 Hz), 4.01
(1H, d, H-10, J¼10.6 Hz), 3.03 (3H, s, CH3N), 2.49 (1H,
s, NCH3), 2.54 (1H, br d, H-30, J¼16.0 Hz), 2.06 (3H, br s,
CH3 at C-50), 1.34 (3H, s, CH3 at C-3), 1.06 (3H, s, CH3 at
C-3); 13C NMR (d, ppm, DMSO-d6) 165.4 (s), 160.1 (s),
156.4 (s), 148.0 (s), 136.8 (s), 126.8 (d, C-5), 120.0 (d,
C-4), 117.3 (d, C-6), 103.9 (d, C-7), 97.6 (s), 89.5 (s, C-2),
50.1 (q, OCH3), 44.9 (s, C-3), 31.4 (t, CH2), 28.4 (q,
NCH3), 28.1 (q, CH3 at C-3), 18.7 (q, at C-3), 10.5 (q, CH3
at C-50); minor component b: 7.22 (1H, s, NH), 6.93 (1H,
d, H-4, J¼7.6 Hz), 6.91 (1H, t, H-6, J¼7.6 Hz), 6.52 (1H, t,
H-5, J¼7.6 Hz), 6.16 (1H, d, H-7, J¼7.6 Hz), 5.36 (2H, br
s, NH2), 3.56 (3H, s, OCH3), 2.94 (1H, br d, H-30,
J¼16.0 Hz), 2.72 (3H, s, NCH3), 2.70 (1H, br d, H-30,
J¼16.0 Hz), 1.99 (3H, s, CH3 at C-50), 1.21 (3H, s, CH3 at
C-3), 1.04 (3H, s, CH3 at C-3); 13C NMR (d, ppm, DMSO-
d6) 165.7 (s), 159.8 (s), 157.2 (br s), 148.2 (s), 135.9 (s),
127.0 (d, C-6), 120.1 (d, C-4), 116.5 (d, C-5), 103.3 (d,
C-7), 96.7 (s), 93.9 (s, C-2), 49.8 (q, OCH3), 45.9 (s, C-3),
29.2 (t, CH2), 28.6 (q, NCH3), 28.0 (q, CH3 at C-3), 19.3
(q, at C-3), 11.4 (q, CH3 at C-50).
m), 2.12 (1H, m), 1.9–0.5 (7H, m), 1.74 (3H, s, CH3C); 13
C
NMR (d, ppm, CDCl3) 156.6 (s, C-2), 146.3 (s), 145.9 (s),
139.1 (s), 128.0 (d), 127.6 (d), 127.4 (d), 126.2 (d), 122.7
(d, C-4), 118.4 (d, C-5), 104.8 (d, C-7), 94.2 (d, C-10), 92.0
(d, CHNO2), 51.9 (s, C-3), 40.2 (d, CHCHNO2), 32.7 (t,
CH2), 31.0 (t, CH2), 29.1 (q, CH3N), 25.7 (q, CH3C), 24.6
1
(t, CH2), 24.1 (t, CH2). Compound cis-32c: H NMR (d,
ppm, CDCl3) 4.48 (1H, m, CHNO2), 4.21 (1H, d, H-10, J¼
11.0 Hz), 3.05 (3H, s, CH3). Compound trans-32d: 1H
NMR (d, ppm, CDCl3) 4.24 (1H, d, H-10, J¼10.2 Hz), 3.94
(1H, dt, CHNO2, J1¼J2¼10.0 Hz, J3¼3.5 Hz, WH¼
29.0 Hz), 3.07 (3H, s, CH3), 2.49 (1H, m), 1.9–0.8 (8H, m),
1.78 (3H, s, CH3C); 13C NMR (d, ppm, CDCl3) 155.9 (s,
C-2), 145.7 (s), 145.2 (s), 138.6 (s), 128.4 (d), 127.6 (d),
126.3 (d), 126.1 (d), 122.6 (d, C-4), 118.4 (d, C-5), 104.9
(d, C-7), 95.2 (d, C-10), 90.5 (d, CHNO2), 51.7 (s, C-3),
39.3 (d, CHCHNO2), 34.6 (t, CH2), 29.9 (t), 29.2 (q,
CH3N), 26.3 (q, CH3C), 24.1 (t, CH2), 23.7 (t, CH2).
4.6.3. 2,20,3,30-Tetrahydro-1,3,3,50-tetramethyl-40-
methoxycarbonyl-10 methoxycarbonylaminospiro
[1H-indole-2,20-pyrrole] (34). Yield 93%; pink solid;
mp 182–185 ꢀC; IR (cmꢂ1, Nujol) 3280, 1753, 1645, 1604,
1463, 1388, 1197, 1135, 999, 893, 749; EIMS (m/z) 359
ꢃ
4.6. Reactions of 2-methyleneindolines (1–3) with 1,2-
diaza-1,3-butadienes (11–13)
(M+ , 82), 285 (100); Anal. Calcd for C19H25N3O4: C,
63.49; H, 7.01; N, 11.69. Found: C, 63.26; H, 7.18; N,
11.53. The isomers 34a and 34b were obtained in 55:45 ratio
by using DMSO-d6 as a solvent (determined by H NMR).
1
4.6.1. General procedure. To a stirred solution of the appro-
priate 1,2-diaza-1,3-butadienes 11–1332 (0.85 mmol) in THF
(5 ml) the substrates1–3 (0.94 mmol) wasadded. Themixture
was allowed to stand at room temperature for 2 h and then the
solventwas evaporatedunder reduced pressure. Theresulting
products 33–40 were isolated by chromatography on silica
gel column with cyclohexane–ethyl acetate (90:10 v/v) and
then purified by crystallization from diethyl ether.
For clarity sake the NMR values are given separately for
each isomer. Major component a: 1H NMR (d, ppm,
DMSO-d6) 8.24 (1H, s, NH), 6.95 (1H, t, H-6, J¼7.6 Hz),
6.86 (1H, d, H-4, J¼7.6 Hz), 6.54 (1H, t, H-5, J¼7.6 Hz),
6.33 (1H, d, H-7, J¼7.6 Hz), 3.59 (3H, s, OCH3), 3.32 (3H,
s, OCH3), 2.98 (1H, br d, J¼16.4 Hz, H-30), 2.64 (3H, s,
NCH3), 2.59 (1H, br d, J¼16.4 Hz, H-30), 2.02 (3H, br s,
CH3 at C-50), 1.30 (3H, s, CH3 at C-3), 1.05 (3H, s, CH3 at
C-3); 13C NMR (d, ppm, DMSO-d6) 165.4 (s), 158.9 (s),
155.6 (s), 147.8 (s), 136.5 (s), 126.9 (d, C-5), 120.0 (d,
C-4), 117.2 (d, C-6), 103.9 (d, C-7), 97.8 (s), 90.8 (s, C-2),
51.8 (q, OCH3), 50.3 (q, OCH3), 45.2 (s, C-3), 30.9 (t,
CH2), 28.1 (q, NCH3), 28.0 (q, CH3 at C-3), 18.2 (q, at
4.6.2. 2,20,3,30-Tetrahydro-1,3,3,50-tetramethyl-40-meth-
oxycarbonyl-10-ureidospiro[1H-indole-2,20-pyrroꢂle1]
(33). Yield 88%; pale pink solid; mp 203–206 ꢀC; IR (cm
,
Nujol) 3465, 3281, 3201, 1693, 1661, 1486, 1321, 1143, 892,
747. 1H NMR (d, ppm, CDCl3) 7.09 (1H, t, J¼7.6 Hz, H-6),
6.97 (1H, d, J¼7.6 Hz, H-4), 6.73 (1H, t, J¼7.6 Hz, H-5),
6.34 (1H, d, J¼7.6 Hz, H-7), 5.24 (1H, s, NH), 4.79 (2H, br
s, NH2), 3.75 (3H, s, OCH3), 3.03 (1H, dq, H-30,
J1¼16.5 Hz, J2¼2.2 Hz), 2.76 (1H, br d, H-30, J¼16.5 Hz),
2.68 (3H, s, NCH3), 2.23 (3H, br s, CH3 at C-30), 1.40 (3H,
s, CH3 at C-3), 1.21 (3H, s, CH3 at C-3); 13C NMR (d,
ppm, CDCl3) 166.0 (s), 158.9 (s), 157.1 (s), 147.6 (s),
136.3 (s), 128.0 (d, C-6), 120.9 (d, C-4), 119.0 (d, C-5),
103.6 (d, C-7), 99.2 (s), 93.4 (s, C-2), 50.9 (q, OCH3), 45.1
(s, C-3), 31.7 (t, CH2), 29.7 (q, NCH3), 28.6 (q, CH3 at C-
3), 20.2 (q, at C-3), 10.8 (q, CH3 at C-50); EIMS (m/z) 344
1
C-3), 10.4 (q, CH3 at C-50); minor component b: H NMR
(d, ppm, DMSO-d6) 8.55 (1H, s, NH), 6.91 (1H, d, H-4,
J¼7.6 Hz), 6.90 (1H, t, H-6, J¼7.6 Hz), 6.51 (1H, t, H-5,
J¼7.6 Hz), 6.14 (1H, d, H-7, J¼7.6 Hz), 3.57 (3H, s,
OCH3), 3.39 (3H, s, OCH3), 2.95 (1H, br d, H-30,
J¼16.4 Hz), 2.71 (3H, s, NCH3), 2.69 (1H, br d, H-30,
J¼16.4 Hz), 1.98 (3H, s, CH3 at C-50), 1.24 (3H, s, CH3 at
C-3), 1.03 (3H, s, CH3 at C-3); 13C NMR (d, ppm, DMSO-
d6) 165.6 (s), 158.6 (s), 156.0 (br s), 148.2 (s), 136.2 (s),
126.8 (d, C-6), 120.1 (d, C-4), 116.7 (d, C-5), 102.9 (d,
C-7), 96.9 (s), 94.1 (s, C-2), 51.8 (q, OCH3), 50.0 (q,
OCH3), 45.8 (s, C-3), 29.3 (t, CH2), 28.5 (q, NCH3), 27.9
(q, CH3 at C-3), 18.8 (q, at C-3), 11.0 (q, CH3 at C-50).
ꢃ
(M+ , 65), 285 (100); Anal. Calcd for C18H24N4O3: C,
62.77; H, 7.02; N, 16.27. Found: C, 62.54; H, 7.13; N,
16.30. The isomers 33a and 33b were obtained in 60:40 ratio
by using DMSO-d6 as a solvent (determined by H NMR).
1
4.6.4. 2,20,3,30-Tetrahydro-1,3,3,50-tetramethyl-40-
methoxycarbonyl-10-tert-butoxycarbonylaminospiro[2H-
indole-2,20-pyrrole] (35). Yield 85%; pale pink solid; mp
164–167 ꢀC; IR (cmꢂ1, Nujol) 3253, 1744, 1643, 1605,
For clarity sake the NMR values are given separately for
each isomer. Major component a: 1H NMR (d, ppm,
DMSO-d6) 6.96 (1H, t, H-6, J¼7.6 Hz), 6.94 (1H, s, NH),
6.87 (1H, d, H-4, J¼7.6 Hz), 6.55 (1H, t, H-5, J¼7.6 Hz),
6.34 (1H, d, H-7, J¼7.6 Hz), 5.72 (2H, br s, NH2), 3.59
(3H, s, OCH3), 2.97 (1H, br d, H-30, J¼16.0 Hz), 2.60 (3H,
ꢃ
1453, 1377, 1133, 989, 892, 741; EIMS (m/z) 401 (M+ ,
73), 301 (31), 285 (100); Anal. Calcd for C22H31N3O4: C,
65.81; H, 7.78; N, 10.47. Found: C, 65.97; H, 7.57; N,

6432
O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
10.32. The isomers 35a and 35b were obtained in 50:50 ratio
by using DMSO-d6 as a solvent (determined by H NMR).
C-3), 31.1 (t, CH2), 30.8 (t, CH2), 27.9 (q, NCH3), 16.3 (q,
at C-3), 11.4 (q, CH3 at C-50), 8.6 (q, CH3 at C-3).
1
For clarity sake the NMR values are given separately for
each isomer. Component a: H NMR (d, ppm, DMSO-d6)
1
4.6.6. 2,20,3,30-Tetrahydro-3-ethyl-1,3,50-trimethyl-40-
methoxycarbonyl-10-methoxycarbonylaminospiro[1H-
indole-2,20-pyrrole] (37). Yield 96%; pale pink solid; mp
168–171 ꢀC; IR (cmꢂ1, Nujol) 3262, 1751, 1648, 1612,
1484, 1368, 1224, 1140, 1013, 889, 761; EIMS (m/z) 373
7.80 (1H, s, NH), 6.96 (1H, t, H-6, J¼7.6 Hz), 6.85 (1H, d,
H-4, J¼7.6 Hz), 6.51 (1H, t, H-5, J¼7.6 Hz), 6.34 (1H, d,
H-7, J¼7.6 Hz), 3.58 (3H, s, OCH3), 2.96 (1H, br d, H-30,
J¼16.4 Hz), 2.63 (3H, s, NCH3), 2.58 (1H, br d, H-30,
J¼16.4 Hz), 2.01 (3H, br s, CH3 at C-50), 1.32 (3H, s, CH3
at C-3), 1.19 (9H, s, C(CH3)3), 1.04 (3H, s, CH3 at C-3);
13C NMR (d, ppm, DMSO-d6) 165.4 (s), 159.1 (s), 154.4
(s), 148.2 (s), 136.5 (s), 126.8 (d, C-5), 119.8 (d, C-4),
117.2 (d, C-6), 103.9 (d, C-7), 97.9 (s), 90.5 (s, C-2), 79.1
(s, C(CH3)3), 50.1 (q, OCH3), 45.8 (s, C-3), 30.8 (t, CH2),
28.2 (q, NCH3), 28.0 (q, CH3 at C-3), 27.9 (q, C(CH3)3),
ꢃ
(M+ , 91), 358 (21), 312 (20), 299 (100); Anal. Calcd for
C20H27N3O4: C, 64.32; H, 7.29; N, 11.25. Found: C, 64.44;
H, 7.18; N, 11.19. The isomers 37a and 37b were obtained
in 50:50 ratio by using DMSO-d6 as a solvent (determined
by 1H NMR). For clarity sake the NMR values are given sep-
1
arately for each isomer. Component a: H NMR (d, ppm,
DMSO-d6) 8.14 (1H, s, NH), 6.92 (1H, t, H-6, J¼7.6 Hz),
6.84 (1H, d, H-4, J¼7.6 Hz), 6.54 (1H, t, H-5, J¼7.6 Hz),
6.32 (1H, d, H-7, J¼7.6 Hz), 3.59 (3H, s, OCH3), 3.32 (3H,
s, OCH3), 2.95 (1H, br d, H-30, J¼16.0 Hz), 2.64 (1H, br d,
H-30, J¼16.0 Hz), 2.63 (3H, s, NCH3), 1.99 (3H, br s, CH3
at C-50), 1.41 (2H, q, CH2 at C-3, J¼7.6 Hz), 1.18 (3H, s,
CH3 at C-3), 0.59 (3H, t, CH3 at C-3); 13C NMR (d, ppm,
DMSO-d6) 165.3 (s), 158.7 (s), 155.5 (s), 148.4 (s), 133.2
(s), 126.8 (d, C-5), 121.5 (d, C-4), 116.5 (d, C-6), 103.8 (d,
C-7), 98.7 (s), 90.9 (s, C-2), 51.8 (q, OCH3), 50.2 (q,
OCH3), 48.6 (s, C-3), 30.7 (t, CH2), 28.8 (t, CH2), 28.0 (q,
NCH3), 15.9 (q, at C-3), 10.4 (q, CH3 at C-50), 8.6 (q, CH3
1
18.6 (q, at C-3), 10.5 (q, CH3 at C-50); component b: H
NMR (d, ppm, DMSO-d6) 8.29 (1H, s, NH), 6.90 (1H, d,
H-4, J¼7.6 Hz), 6.89 (1H, t, H-6, J¼7.6 Hz), 6.51 (1H, t,
H-5, J¼7.6 Hz), 6.13 (1H, d, H-7, J¼7.6 Hz), 3.56 (3H, s,
OCH3), 2.93 (1H, br d, H-30, J¼16.4 Hz), 2.71 (3H, s,
NCH3), 2.68 (1H, br d, H-30, J¼16.4 Hz), 1.96 (3H, s, CH3
at C-50), 1.22 (3H, s, CH3 at C-3), 1.19 (9H, s, C(CH3)3),
1.02 (3H, s, CH3 at C-3); 13C NMR (d, ppm, DMSO-d6)
165.6 (s), 158.8 (s), 154.0 (s), 147.8 (s), 136.2 (s), 126.7 (d,
C-6), 119.9 (d, C-4), 116.4 (d, C-5), 103.1 (d, C-7), 96.7
(s), 93.6 (s, C-2), 79.2 (s, C(CH3)3), 49.8 (q, OCH3), 45.2
(s, C-3), 29.4 (t, CH2), 28.4 (q, NCH3), 27.9 (q, CH3 at
C-3), 27.8(q, C(CH3)3), 18.1(q, at C-3), 11.0 (q, CH3 at C-50).
1
at C-3); component b: H NMR (d, ppm, DMSO-d6) 8.51
(1H, s, NH), 6.98 (1H, t, H-6, J¼7.6 Hz), 6.80 (1H, d, H-4,
J¼7.6 Hz), 6.51 (1H, t, H-5, J¼7.6 Hz), 6.13 (1H, d, H-7,
J¼7.6 Hz), 3.58 (3H, s, OCH3), 3.38 (3H, s, OCH3), 2.95
(1H, br d, H-30, J¼16.0 Hz), 2.74 (1H, br d, H-30,
J¼16.0 Hz), 2.68 (3H, s, NCH3), 2.03 (3H, s, CH3 at C-50),
1.42 (2H, q, CH2 at C-3, J¼7.6 Hz), 1.26 (3H, s, CH3 at C-
3), 0.57 (3H, t, CH3 at C-3); 13C NMR (d, ppm, DMSO-d6)
165.6 (s), 158.4 (s), 155.9 (s), 148.7 (s), 132.9 (s), 127.0 (d,
C-6), 121.6 (d, C-4), 116.0 (d, C-5), 102.6 (d, C-7), 97.4
(s), 94.2 (s, C-2), 51.7 (q, OCH3), 49.9 (q, OCH3), 49.1 (s,
C-3), 30.9 (t, CH2), 30.4 (t, CH2), 27.9 (q, NCH3), 15.8 (q,
at C-3), 11.0 (q, CH3 at C-50), 8.5 (q, CH3 at C-3).
4.6.5. 2,20,3,30-Tetrahydro-3-ethyl-1,3,50-trimethyl-40-
methoxycarbonyl-10-ureidospiro[2H-indole-2,20-pyr-
role] (36). Yield 87%; white solid; mp 171–174 ꢀC; IR
(cmꢂ1, Nujol) 3431, 3340, 3284, 1673, 1621, 1463, 1446,
ꢃ
1333, 1145, 887, 743; EIMS (m/z) 358 (M+ , 58), 299
(100), 262 (100); Anal. Calcd for C19H26N4O3: C, 63.67;
H, 7.31; N, 15.63. Found: C, 63.74; H, 7.19; N, 15.79. The
isomers 36a and 36b were obtained in 60:40 ratio by using
DMSO-d6 as a solvent (determined by 1H NMR). For clarity
sake the NMR values are given separately for each isomer.
1
Major component a: H NMR (d, ppm, DMSO-d6) 6.97
(1H, t, H-6, J¼7.6 Hz), 6.84 (1H, s, NH), 6.80 (1H, d, H-
4, J¼7.6 Hz), 6.54 (1H, t, H-5, J¼7.6 Hz), 6.33 (1H, d, H-
7, J¼7.6 Hz), 5.63 (2H, br s, NH2), 3.59 (3H, s, OCH3),
2.97 (1H, br d, H-30, J¼16.0 Hz), 2.59 (1H, br d, H-30,
J¼16.0 Hz), 2.58 (3H, s, NCH3), 2.05 (3H, br s, CH3 at C-
50), 1.42 (2H, q, CH2 at C-3, J¼7.6 Hz), 1.27 (3H, s, CH3
at C-3), 0.59 (3H, t, CH3 at C-3); 13C NMR (d, ppm,
DMSO-d6) 165.4 (s), 159.9 (s), 156.4 (s), 148.6 (s), 133.6
(s), 126.9 (d, C-5), 121.5 (d, C-4), 116.7 (d, C-6), 103.7
(d, C-7), 98.3 (s), 89.4 (s, C-2), 50.1 (q, OCH3), 48.3 (s,
C-3), 31.1 (t, CH2), 28.7 (t, CH2), 28.4 (q, NCH3), 16.7 (q,
at C-3), 10.4 (q, CH3 at C-50), 8.6 (q, CH3 at C-3); minor
4.6.7. 1,20,3,30-Tetrahydro-3-ethyl-1,3,40-trimethyl-
50-methoxycarbonyl-10-tert-butoxycarbonylamino-
spiro[2H-indole-2,20-pyrrole] (38). Yield 85%; pink solid;
mp 138–141 ꢀC; IR (cmꢂ1, Nujol) 3248, 1738, 1650, 1602,
ꢃ
1458, 1367, 1271, 1135, 891, 783; EIMS (m/z) 415 (M+ ,
63), 315 (31), 299 (100); Anal. Calcd for C20H27N3O4: C,
64.32; H, 7.29; N, 11.25. Found: C, 64.44; H, 7.18; N,
11.19. The isomers 38a and 38b were obtained in 50:50 ratio
1
by using DMSO-d6 as a solvent (determined by H NMR).
For clarity sake the NMR values are given separately for
each isomer. Component a: H NMR (d, ppm, DMSO-d6)
1
7.67 (1H, s, NH), 6.98 (1H, t, H-6, J¼7.6 Hz), 6.79 (1H, d,
H-4, J¼7.6 Hz), 6.55 (1H, t, H-5, J¼7.6 Hz), 6.33 (1H, d,
H-7, J¼7.6 Hz), 3.59 (3H, s, OCH3), 2.95 (1H, br d, H-30,
J¼16.0 Hz), 2.66 (1H, br d, H-30, J¼16.0 Hz), 2.62 (3H, s,
NCH3), 2.01 (3H, br s, CH3 at C-50), 1.40 (2H, q, CH2 at
C-3, J¼7.6 Hz), 1.27 (3H, s, CH3 at C-3), 1.20 (9H, s,
C(CH3)3), 0.59 (3H, t, CH3 at C-3); 13C NMR (d, ppm,
DMSO-d6) 165.3 (s), 159.0 (s), 154.3 (s), 148.8 (s), 133.3
(s), 126.8 (d, C-5), 121.5 (d, C-4), 116.5 (d, C-6), 103.7
(d, C-7), 98.8 (s), 93.8 (s, C-2), 79.0 (s, C(CH3)3), 50.1 (q,
OCH3), 49.1 (s, C-3), 30.7 (t, CH2), 30.2 (t, CH2), 28.0 (q,
NCH3), 27.8 (q, C(CH3)3), 15.6 (q, at C-3), 10.4 (q, CH3
1
component b: H NMR (d, ppm, DMSO-d6) 7.19 (1H, s,
NH), 6.92 (1H, t, H-6, J¼7.6 Hz), 6.86 (1H, d, H-4,
J¼7.6 Hz), 6.51 (1H, t, H-5, J¼7.6 Hz), 6.14 (1H, d, H-7,
J¼7.6 Hz), 5.33 (2H, br s, NH2), 3.55 (3H, s, OCH3), 2.93
(1H, br d, H-30, J¼16.0 Hz), 2.73 (1H, br d, H-30,
J¼16.0 Hz), 2.68 (3H, s, NCH3), 1.98 (3H, s, CH3 at C-
50), 1.41 (2H, q, CH2 at C-3, J¼7.6 Hz), 1.14 (3H, s, CH3
at C-3), 0.55 (3H, t, CH3 at C-3); 13C NMR (d, ppm,
DMSO-d6) 165.7 (s), 159.6 (s), 157.1 (s), 148.8 (s), 132.5
(s), 127.1 (d, C-6), 121.5 (d, C-4), 115.8 (d, C-5), 102.9
(d, C-7), 97.0 (s), 93.8 (s, C-2), 49.7 (q, OCH3), 49.2 (s,

O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
6433
at C-50), 8.6 (q, CH3 at C-3); component b: 1H NMR (d, ppm,
DMSO-d6) 8.26 (1H, s, NH), 6.90 (1H, t, H-6, J¼7.6 Hz),
6.84 (1H, d, H-4, J¼7.6 Hz), 6.51 (1H, t, H-5, J¼7.6 Hz),
6.12 (1H, d, H-7, J¼7.6 Hz), 3.57 (3H, s, OCH3), 2.94
(1H, br d, H-30, J¼16.0 Hz), 2.72 (1H, br d, H-30,
J¼16.0 Hz), 2.69 (3H, s, NCH3), 1.97 (3H, s, CH3 at C-
50), 1.41 (2H, q, CH2 at C-3, J¼7.6 Hz), 1.20 (9H, s,
C(CH3)3), 1.16 (3H, s, CH3 at C-3), 0.56 (3H, t, CH3 at C-
3); 13C NMR (d, ppm, DMSO-d6) 165.5 (s), 158.7 (s),
154.0 (s), 148.4 (s), 132.8 (s), 126.8 (d, C-6), 121.5 (d, C-
4), 115.8 (d, C-5), 102.8 (d, C-7), 97.1 (s), 90.6 (s, C-2),
79.2 (s, C(CH3)3), 49.8 (q, OCH3), 48.6 (s, C-3), 30.8 (t,
CH2), 28.9 (t, CH2), 28.0 (q, NCH3), 27.9 (q, C(CH3)3),
15.9 (q, at C-3), 11.0 (q, CH3 at C-50), 8.5 (q, CH3 at C-3).
2.46 (1H, br d, H-30, J¼16.0 Hz), 2.05 (3H, br s, CH3 at
C-50), 1.88 (1H, br d, H-30, J¼16.0 Hz), 1.71 (3H, s, CH3
at C-3), 1.28 (9H, s, C(CH3)3). 13C NMR (d, ppm, DMSO-
d6) 165.1 (s), 158.6 (s), 154.9 (s), 149.6 (s), 144.8 (s),
135.9 (s), 127.7 (s), 127.6 (s), 127.3 (s), 126.2 (d, C-5),
121.8 (d, C-4), 117.6 (d, C-6), 104.4 (d, C-7), 98.1 (s),
94.4 (s, C-2), 79.5 (s, C(CH3)3), 53.7 (q, OCH3), 50.0 (s,
C-3), 33.2 (t, CH2), 28.4 (q, NCH3), 27.9 (q, C(CH3)3),
19.0 (q, CH3 at C-3), 10.5 (q, CH3 at C-50); minor component
b: 1H NMR (d, ppm, DMSO-d6) 8.55 (1H, s, NH), 7.23–7.00
(6H, m, Ph+H-6), 6.77 (1H, d, H-4, J¼7.6 Hz), 6.53 (1H, t,
H-5, J¼7.6 Hz), 6.31 (1H, d, H-7, J¼7.6 Hz), 3.32 (3H, s,
OCH3), 2.70 (3H, s, NCH3), 2.43 (1H, br d, H-30,
J¼16.0 Hz), 2.10 (1H, br d, H-30, J¼16.0 Hz), 1.99 (3H, s,
CH3 at C-50), 1.67 (3H, s, CH3 at C-3), 1.27 (9H, s,
C(CH3)3); 13C NMR (d, ppm, DMSO-d6) 165.4 (s), 159.1
(s), 154.4 (br s), 149.6 (s), 144.6 (s), 135.9 (s), 127.9 (s),
127.8 (s), 127.1 (s), 126.2 (d, C-6), 121.6 (d, C-4), 117.0
(d, C-5), 103.4 (d, C-7), 97.1 (s), 91.1 (s, C-2), 79.5 (s,
C(CH3)3), 53.0 (q, OCH3), 49.8 (s, C-3), 31.4 (t, CH2),
28.1 (q, NCH3), 28.0 (q, C(CH3)3), 17.3 (q, CH3 at C-3),
11.2 (q, CH3 at C-50).
4.6.8. 2,203,30-Tetrahydro-1,3,50-trimethyl-40-methoxy-
carbonyl-3-phenyl-10-ureidospiro[1H-indole-2,20-pyr-
role] (39). Yield 94%; white solid; mp 144–147 ꢀC; IR
(cmꢂ1, Nujol) 3428, 3285, 3173, 1666, 1606, 1493, 1440,
ꢃ
1363, 1319, 1200, 890, 782; EIMS (m/z) 406 (M+ , 74),
347 (100); Anal. Calcd for C23H26N4O3: C, 67.96; H,
6.45; N, 13.78. Found: C, 67.81; H, 6.50; N, 13.84. The iso-
mers 39a and 39b were obtained in 65:35 ratio by using
DMSO-d6 as a solvent (determined by 1H NMR). For clarity
sake the NMR values are given separately for each isomer.
Acknowledgements
1
Major component a: H NMR (d, ppm, DMSO-d6) 7.25-
6.73 (8H, m, Ph+NH+H-4+H-6), 6.57 (1H, t, H-5,
J¼7.6 Hz), 6.50 (1H, d, H-7, J¼7.6 Hz), 5.92 (2H, br s,
NH2), 3.46 (3H, s, OCH3), 2.62 (3H, s, NCH3), 2.43 (1H,
br d, H-30, J¼16.0 Hz), 2.09 (3H, br s, CH3 at C-50), 1.82
(1H, br d, H-30, J¼16.0 Hz), 1.75 (3H, s, CH3 at C-3); 13C
NMR (d, ppm, DMSO-d6) 165.2 (s), 160.1 (s), 156.6 (s),
149.3 (s), 145.2 (s), 136.3 (s), 127.8 (s), 127.7 (s), 127.2
(s), 126.2 (d, C-5), 121.8 (d, C-4), 117.7 (d, C-6), 103.6
(d, C-7), 98.0 (s), 90.0 (s, C-2), 52.7 (q, OCH3), 50.0 (s,
C-3), 33.9 (t, CH2), 28.4 (q, NCH3), 19.3 (q, CH3 at C-50),
Financial supports from M.I.U.R. (Rome), PRIN 2003-2004,
and the Universities of Urbino, Trieste and Bologna are
gratefully acknowledged. Thanks are also given to Dr.
Federico Berti of the Dipartimento di Scienze Chimiche,
`
Universita di Trieste, for molecular modelling calculations.
References and notes
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1
10.6 (q, CH3 at C-3); minor component b: H NMR (d,
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Ph+H-4+H-6), 6.49 (1H, t, H-5, J¼7.6 Hz), 6.34 (1H, d,
H-7, J¼7.6 Hz), 5.53 (2H, br s, NH2), 3.45 (3H, s, OCH3),
2.71 (3H, s, NCH3), 2.36 (1H, br d, H-30, J¼16.0 Hz), 2.17
(1H, br d, H-30, J¼16.0 Hz), 2.01 (3H, s, CH3 at C-50),
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(s), 127.9 (s), 127.7 (s), 127.1 (s), 126.2 (d, C-6), 121.7 (d,
C-4), 117.0 (d, C-5), 104.3 (d, C-7), 97.2 (s), 94.7 (s, C-2),
54.2 (q, OCH3), 49.7 (s, C-3), 31.3 (t, CH2), 28.2 (q,
NCH3), 18.0 (q, CH3 at C-50), 11.5 (q, CH3 at C-3).
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carbonyl-3-phenyl-10-tert-butoxycarbonylamino-
spiro[1H-indole-2,20-pyrrole] (40). Yield 81%; pink solid;
mp 184–187 ꢀC; IR (cmꢂ1, Nujol) 3241, 1763, 1656, 1605,
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ꢃ
1366, 1276, 1161, 1135, 999, 752; EIMS (m/z) 463 (M+ ,
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69.95; H, 7.18; N, 9.06. Found: C, 70.04; H, 7.01; N, 9.25.
The isomers 40a and 40b were obtained in 55:45 ratio by us-
ꢀ
7. Christie, R. M.; Agyako, C.; Mitchell, K.; Lycka, A. Dyes
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1
ing DMSO-d6 as a solvent (determined by H NMR). For
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8.18 (1H, s, NH), 7.23–7.00 (6H, m, Ph+H-6), 6.98 (1H, d,
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H-7, J¼7.6 Hz), 3.46 (3H, s, OCH3), 2.63 (3H, s, NCH3),

6434
O. A. Attanasi et al. / Tetrahedron 62 (2006) 6420–6434
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´
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