Tunable Pd-catalyzed cyclization of indole-2-carboxylic acid allenamides: Carboamination vs microwave-assisted hydroamination

Article abstract of DOI:10.1021/jo101501u

A variety of 3-vinyl-substituted imidazo[1,5-a]indole derivatives were synthesized by intramolecular Pd-catalyzed cyclization of the title allenamides through either a domino carbopalladation/exo-cyclization process or a novel hydroamination reaction that proceeds smoothly under microwave irradiation. Both the observed pathways involve a π-allyl-palladium(II) complex arising from insertion of the allene group into a palladium(II) species, the latter being formed in situ by the intervention of an aryl iodide or of the N-H group. In both cases, the role of nucleophile is covered by the indole nitrogen.

Full text of DOI:10.1021/jo101501u

pubs.acs.org/joc
Tunable Pd-Catalyzed Cyclization of Indole-2-carboxylic Acid
Allenamides: Carboamination vs Microwave-Assisted Hydroamination
Egle M. Beccalli,‡ Alice Bernasconi,‡ Elena Borsini,‡ Gianluigi Broggini,*,§
Micol Rigamonti,§ and Gaetano Zecchi§
‡
ꢀ
DISMAB, Sezione di Chimica Organica “A. Marchesini”, Universita di Milano, via Venezian 21,
20133 Milano, Italy, and §Dipartimento di Scienze Chimiche e Ambientali, Universitaꢀ dell’Insubria,
via Valleggio 11, 22100 Como, Italy
gianluigi.broggini@uninsubria.it
Received July 30, 2010
A variety of 3-vinyl-substituted imidazo[1,5-a]indole derivatives were synthesized by intramolecular
Pd-catalyzed cyclization of the title allenamides through either a domino carbopalladation/
exo-cyclization process or a novel hydroamination reaction that proceeds smoothly under micro-
wave irradiation. Both the observed pathways involve a π-allyl-palladium(II) complex arising from
insertion of the allene group into a palladium(II) species, the latter being formed in situ by the
intervention of an aryl iodide or of the N-H group. In both cases, the role of nucleophile is covered
by the indole nitrogen.
Introduction
and pharmaceutical product synthesis.3 Palladium catalysts
often have been employed for cyclization reactions of allenes
bearing a nucleophilic functionality, leading to exo- or
endo-olefin-containing cyclic compounds (Figure 1, paths
a and b).4,5 In this context, among the different kinds of
For a long time, the reactions of allenes have attracted
much attention due to the peculiar chemical properties
associated with their cumulated double bonds.1 In particu-
lar, during the past decades, an increasing interest has been
placed on transition metal-catalyzed cyclization of function-
alized allenes as a powerful one-step method to prepare
carbo- and heterocycles endowed with highly substituted
olefin groups,2 which can be useful intermediates for natural
(4) For examples of Pd-catalyzed exo-cyclizations of allenes, see: (a)
Franzen, J.; Backvall, J.-E. J. Am. Chem. Soc. 2003, 125, 6056. (b) Walkup,
R. D.; Park, G. Tetrahedron Lett. 1987, 28, 1023. (c) Walkup, R. D.; Mosher,
M. D. Tetrahedron 1993, 49, 9285. (d) Walkup, R. D.; Mosher, M. D.
Tetrahedron Lett. 1994, 35, 8545. (e) Lathbury, D.; Vernon, P.; Gallagher, T.
Tetrahedron Lett. 1986, 27, 6009. (f) Gallagher, T.; Davies, I. W.; Jones,
S. W.; Lathbury, D. J. Chem. Soc., Perkin Trans. 1 1992, 433. (g) Kimura, M.;
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Ma, S.; Gao, W. J. Org. Chem. 2002, 67, 6104. (b) Ma, S.; Yu, Z. Angew.
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T. Chem.;Eur. J. 2007, 13, 1692. (h) Karstens, W. F. J.; Klomp, D.; Rutjes,
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S. Org. Lett. 2007, 9, 1703.
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€
DOI: 10.1021/jo101501u
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Published on Web 09/23/2010
J. Org. Chem. 2010, 75, 6923–6932 6923
2010 American Chemical Society

Beccalli et al.
SCHEME 1. Preparation of the Indole Allenamide 2
JOCArticle
FIGURE 1. Pd-catalyzed exo- and endo-cyclization of nucleophilic
substituted allenes.
1,2-diene derivatives, allenamides have been shown to be
versatile and effective building blocks for generating
nitrogen-containing heterocycles.6
On the basis of our late interest toward the syntheses of
five-membered heterocycles starting from allenes,6f,g,7 as
well as of our ongoing efforts directed to the development
of intramolecular palladium-catalyzed procedures,8 we have
recently reported the domino carbopalladation/5-exo-allylic
amination of R-aminoacid allenamides as a fruitful route to
imidazolidinone derivatives.9
Herein, we describe new results concerning the Pd-cata-
lyzed intramolecular carboamination and hydroamination
of indolyl allenamides leading to vinyl-substituted imidazo-
[1,5-a]indole derivatives, where a pivotal role in determining
the feasibility of the hydroamination process was covered by
the microwave assistance.
boxylic acid through conversion into the propargylamide
1 and following prototropic isomerization promoted by
t-BuOK (Scheme 1). It is crucial for the formation of the
allene 2 to avoid an exposure to the base longer than 1 min, in
order to prevent the nucleophilic attack of the nitrogen atom
to the central carbon of the 1,2-diene moiety giving the
pyrazino[1,2-a]indole 3.
Carboamination Reactions. At first, we examined the
possibility of cyclizing compound 2 by exploiting the known
electrophilic reactivity of a π-allyl-palladium complex such
as 4, easily accessible by carbopalladation of the allene
moiety.10 In the present case, the second step of the domino
process could have been accomplished by either the nitrogen
atom or the C-3 of the indole ring. Under the best conditions
typically used to promote this kind of reaction (1.5 equiv of
PhI, 5 mol % of Pd(PPh3)4, 4.0 equiv of K2CO3), the
cyclization really took place giving the R-styryl imidazo-
[1,5-a]indole derivative 5a (Scheme 2, path A). Among the
array of solvents tested to optimize the reaction (DMF,
DMA, MeCN, dioxane), acetonitrile was proven as the most
effective. The formation of 5a constitutes an overall carbo-
palladation/5-exo-allylic amination process, which is doubly
selective since the π-allyl-palladium complex 4 is trapped
exclusively on its internal carbon atom by the only indole
nitrogen. The scope of this reaction was then explored with
different aryl iodides, thus providing the expected products
5b-e.
Results and Discussion
The paradigmatic allene 2 suitable to our study was
synthesized in near quantitative yields from indole-2-car-
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the rarity of this kind of carboamination reactions on allenes
in carbonylative conditions13 prompted us to perform the
domino heterocyclization of 2 in the presence of carbon
monoxide. By using the same catalyst, base, and solvent,
the allenamide 2 reacted with iodobenzene in CO atmo-
sphere (1 atm) to give compound 7a, even if in modest yield
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JOCArticle
SCHEME 2. Pd-Catalyzed Carboamination and Carbonylative
Amination of Allenamide 2
SCHEME 3. Pd-Catalyzed Heteroyclization of Allenamide 8
rare precedents in the literature.14 To this end, we synthe-
sized the o-iodoaryl-substituted allenamide 8 from the corre-
sponding propargylamide and reacted it with Pd(PPh3)4 and
K2CO3 in acetonitrile. Actually, the reaction gave the pen-
tacyclic imidazolinone derivative 10, which can be ascribed
to intramolecular carbopalladation of the allene group to
form the π-allyl-palladium complex 9 and subsequent in-
tramolecular amination by the indole nitrogen (Scheme 3).
Once again, acetonitrile was essential as the solvent to
maximize the yield of the domino carboamination product
10. In fact, the utilization of DMF provided, beside traces of
the pentacyclic compounds 10 and 12, a high amount of the
pyrazine derivative 11 (Scheme 4, path a). The latter product
can be justified by the direct nucleophilic attack of the
nitrogen atom on the 1,2-diene central carbon, similarly to
what has occurred in the conversion of 2 to 3. The iodo
derivative 11 was proven to be the precursor of 12 by an
independent intramolecular Heck reaction carried out on the
pyrazine double bond following the ligand-free “Jeffery
conditions” (Scheme 4, path b).15 The pentacyclic system
12 was also obtained directly starting from the allene 8 in the
same conditions of path b, which are able to promote both
the amination and the Heck reaction steps (Scheme 4, path c).
Hydroamination Reactions. The results described above
provide an efficient and general entry to imidazo[1,5-
a]indoles bearing in the 3-position a vinyl pendant that in
turn happens to be R-substituted (eventually involving a
further fused-ring). However, we envisaged the possibility
to synthesize more simple substrates having in the 3-position
an unsubstituted vinyl pendant, which are products of a
hydroamination process. Although transition metal-catalyzed
hydroamination reactions of allenes are an attractive atom-
economical route to achieve nitrogen-containing hetero-
cycles,16 the examples of the Pd-catalyzed processes remain
scarcely reported in the literature.17 In the search for new
conditions to this purpose, we investigated the behavior of the
indolyl allenamide 2 under microwave irradiation.18,19 We
found that the microwave activation is able to provide
a 5-exo-allylic hydroamination in the presence solely of
due to the presence of degradation products, having the
imidazo[1,5-a]indole skeleton bearing an enone moiety
(Scheme 2, path B). This reaction gave the best results
working at room temperature for a prolonged time; in fact,
by refluxing the mixture for 24 h an increased amount of
carboamination product 5a was formed. The reaction of
compound 2 with 4-nitroiodobenzene under the same con-
ditions at room temperature took place with formation of the
carboamination compound 5e, and no carbonylation pro-
duct was detected. A reasonable step sequence leading to the
products 7a-d involves (i) carbonylation of the first-formed
PhPd(II)I species to give the PhCOPdI complex and
(ii) addition of the latter to the central carbon of the 1,2-
diene group to form the aroyl intermediate 6, which then
undergoes the 5-exo-allylic cyclization to 7.
The further stage of our investigation was directed to
realize a totally intramolecular version of the domino allene
carboamination described above, a kind of process that finds
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J. Org. Chem. Vol. 75, No. 20, 2010 6925

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JOCArticle
SCHEME 4. Competitive Cyclizations of Allenamide 8
SCHEME 5. Intramolecular Cyclizations of Allenamide 2 under
Microwave Irradiation
different NH groups (i.e., amines, amides, and pyrrole), an
initial coordination of the Pd(0) catalyst with the indole
nitrogen can give the Pd(II)-hydride complex A (Figure 2).20
Pd(PPh3)4 as catalyst, affording the desired vinyl derivative 13
(Scheme 5). Both palladium catalyst and microvawe irradia-
tion are necessary to promote the 5-exo-allylic hydroamination
of indole allenamide 2. In fact, heating 2 in the absence of
microwave activation, only a tarry mixture due to degradation
processes was obtained. Conversely, the lack of the palladium
catalyst afforded the formation of the hydroxy-substituted
pyrazino[1,2-a]indole 14 (41%). This latter arises from 3 by a
formal addition of water and, however, the use of microwave
activation is not essential, being achievable in 38% yield also
by heating a solution of 2 in toluene.
Gratifyingly, a similar trend of reactivity was observed in
analogous preparative reactions carried out on several indole
allenamides variously substituted on the phenyl ring as
well as on the amide nitrogen. Actually, the substrates
15a-i afforded the vinyl compounds 16a-i in satisfactory
to high yields (Table 1).
FIGURE 2. Proposed mechanistic cycle.
Such an intermediate would be susceptible to insertion of the
allene group into the Pd-H bond to generate the π-allyl-
Pd(II) complex B, which in turn would undergo the intra-
molecular formation of the new carbon-nitrogen bond and
the subsequent reductive elimination of a Pd(0) species.
As a support for the proposed mechanism, we found that
the deuterated hydroamination product 18 was formed in
the cyclization of the deuterium-substituted allene 17, pre-
pared by treatment of a solution of 2 in CDCl3 with D2O
(Scheme 6).
On comparing the carboamination and hydroamination
pathways going from 2 to 5a-e and 13 respectively, one can
note that both of them involve the attack of the indole
nitrogen to the inner carbon of a π-allyl-Pd(II) unity.
However, the origin of the latter species is different in the
two cases. In the first case, the π-allyl-Pd(II) intermediate is
In view of its novelty, the observed hydroamination reac-
tion of the allenamides 2 and 15a-i deserves a mechanistic
picture. Similarly to what was previously reported for
(18) For recent reviews and books on microwave-assisted organic synth-
esis, see: (a) Kappe, O. C. Angew. Chem., Int. Ed. 2004, 43, 6250. (b) Loupy,
A. Microwaves in Organic Synthesis, 2nd ed.; Wiley-VCH: Weinheim,
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41, 629. (d) Pineiro, M.; Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2009,
5287. (e) Caddick, S.; Fitzmaurice, R. Tetrahedron 2009, 65, 3325.
(19) For recent reviews on Pd-catalyzed reactions by microwave activa-
tion, see: (a) Appukkuttan, P.; Van der Eycken, E. Eur. J. Org. Chem. 2008,
1133. (b) Barge, A.; Tagliapietra, S.; Tei, L.; Cintas, P.; Cravotto, G. Curr.
Org. Chem. 2008, 12, 1588. For recent examples of Pd-catalyzed reactions by
microwave activation, see: (c) Tsukamoto, H.; Matsumoto, T.; Kondo, Y.
J. Am. Chem. Soc. 2008, 130, 388. (d) Beccalli, E. M.; Broggini, G.;
Martinelli, M.; Sottocornola, S. Synthesis 2008, 136. (e) Beccalli, E. M.;
Broggini, G.; Martinelli, M.; Paladino, G.; Rossi, E. Synthesis 2006, 2404. (f)
Andaloussi, M.; Lindh, J.; Saevmarker, J.; Sjoeberg, P. J. R.; Larhed, M.
Chem.;Eur. J. 2009, 15, 13069. (g) Roberts, B.; Liptrot, D.; Alcaraz, L. Org.
Lett. 2010, 12, 1264. (h) Reichelt, A.; Falsey, J. R.; Rzasa, R. M.; Thiel, O. R.;
Achmatowicz, M. M.; Larsen, R. D.; Zhang, D. Org. Lett. 2010, 12, 792.
(20) (a) Tsuji, J. In Palladium Reagents and Catalysts;New Perspectives
for the 21st Century; John Wiley & Sons, Ltd: Hoboken, NJ, 2004; pp 527,
538, 569, and 605. (b) Muller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675. (c)
Yamamoto, Y.; Radhakrishnan, U. Chem. Soc. Rev. 1999, 28, 199. (d)
Seligson, A. L.; Cowan, R. L.; Trogler, W. C. Inorg. Chem. 1991, 30, 3371.
(e) Fafard, C. M.; Adhikari, D.; Foxman, B. M.; Mindiola, D. J.; Ozerov,
O. V. J. Am. Chem. Soc. 2007, 129, 10318. (f) Ozerov, O. V.; Guo, C.; Fan, L.;
Foxman, B. M. Organometallics 2004, 23, 5573. (g) Fan, L.; Foxman, B. M.;
Ozerov, O. V. Organometallics 2004, 23, 326. (h) Macchioni, A.; Romani, A.;
Zuccaccia, C.; Guglielmetti, G.; Querci, C. Organometallics 2003, 22, 1526.
(i) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Paladino, G. Tetrahedron
2005, 61, 1077. (j) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J. Org. Chem.
1998, 63, 6458. (k) Shi, M.; Chen, Y.; Xu, B. Org. Lett. 2003, 5, 1225. (l)
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TABLE 1. Scope of the Reaction
J. Org. Chem. Vol. 75, No. 20, 2010 6927

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SCHEME 6. Pd-Catalyzed Hydroamination of Deuterated
Indole Allenamides
N-(2-Iodobenzyl)-N-propargyl-1H-indole-2-carboxamide: yield
84%, white solid, mp 173 °C (i-Pr2O); IR 3310, 3227, 2123, 1670
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.38 (1H, s), 4.44 (2H, s),
5.03 (2H, s), 7.07-7.14 (2H, m), 7.27-7.46 (5H, m), 7.63-7.69
(1H, m), 7.95-7.97 (1H, m), 9.62 (1H, br s); 13C NMR (100 MHz,
CDCl3) δ 38.3 (t), 49.7 (t), 73.2 (d), 78.0 (s), 87.1 (s), 104.9 (d),
111.1 (d), 119.8 (d), 120.7 (d), 121.7 (d), 127.4 (d), 128.6 (d), 129.5
(d), 131.3 (s) 138.5 (s), 139.1 (d), 139.8 (s), 146.1 (s), 162.3 (s); MS
m/z 414 (Mþ). Anal. Calcd for C19H15IN2O: C, 55.09; H, 3.65; N,
6.76. Found: C, 55.15; H, 3.42; N, 6.55.
N-Methyl-N-propargyl-5-methoxy-1H-indole-2-carboxamide:
yield 94%, white solid, mp 143 °C (i-Pr2O); IR 3305, 3224, 2114,
due to a rather common reaction between the allene function
and the first-formed PhPd(II)I, while in the second case the
Pd(0)-catalyst acts at the indole NH group and the subse-
quent hydride transfer on the allene function generates the
π-allyl-Pd(II) intermediate.
1
1658 cm-1; H NMR (400 MHz, CDCl3) δ 2.38 (1H, s), 3.20
(3H, s), 3.85 (3H, s), 4.48 (2H, s), 6.91 (1H, s), 6.96 (1H, d, J =
8.9 Hz), 7.08 (1H, s), 7.37 (1H, d, J = 8.9 Hz), 9.95 (1H, br s);
13C NMR (100 MHz, CDCl3) δ 38.7 (q), 45.8 (t), 55.7 (q), 74.5
(d), 78.6 (s), 102.3 (d), 105.7 (d), 112.9 (d), 116.0 (d), 127.9 (s),
129.3 (s), 131.4 (s), 154.5 (s), 163.2 (s); MS m/z 242 (Mþ). Anal.
Calcd for C14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C,
69.22; H, 5.98; N, 11.69.
N-Methyl-N-propargyl-5-methyl-1H-indole-2-carboxamide:
yield 65%, white solid, mp 136 °C (i-Pr2O); IR 3312, 3220,
2118, 1664 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.39 (1H, s),
2.47 (3H, s), 3.41 (3H, s), 4.50 (2H, s), 6.93 (1H, s), 7.14 (1H, d,
J = 8.4 Hz), 7.39 (1H, d, J = 8.4 Hz), 7.46 (1H, s), 10.09 (1H, br
s); 13C NMR (100 MHz, CDCl3) δ 21.5 (q), 39.4 (q), 46.1 (t),
73.6 (d), 78.6 (s), 105.6 (d), 111.7 (d), 121.3 (d), 126.5 (d), 127.9
(s), 128.9 (s), 129.7 (s), 134.5 (s), 163.3 (s); MS m/z 226 (Mþ).
Anal. Calcd for C14H14N2O: C, 74.31; H, 6.24; N, 12.38.
Found: C, 74.56; H, 6.12; N, 12.45.
N-Methyl-N-propargyl-5-chloro-1H-indole-2-carboxamide: yield
65%, white solid, mp 152 °C (i-Pr2O); IR 3307, 3235, 2120, 1673
cm-1;1H NMR (400 MHz, CDCl3) δ2.39 (1H, s), 3.43 (3H, s), 4.48
(2H, s), 6.92 (1H, s), 7.24 (1H, d, J = 8.7 Hz), 7.40 (1H, d, J = 8.7
Hz), 7.64 (1H, s), 10.03 (1H, br s); 13C NMR (100 MHz, CDCl3)
δ 33.4 (q), 47.8 (t), 72.8 (d), 78.3 (s), 105.5 (d), 111.7 (d), 121.3 (d),
126.5 (d), 127.9 (s), 128.9 (s), 129.7 (s), 134.5 (s), 163.3 (s); MS m/z
246 (Mþ). Anal. Calcd for C13H11ClN2O: C, 63.29; H, 4.49; N,
11.36. Found: C, 63.01; H, 4.62; N, 11.58.
N-Methyl-N-propargyl-7-nitro-1H-indole-2-carboxamide: yield
74%, white solid, mp 161 °C (i-Pr2O); IR 3315, 3216, 2112, 1664
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.39 (1H, s), 3.12 (3H, s),
4.45 (2H, s), 7.10 (1H, s), 7.27 (1H, dd, J = 7.8 Hz, 7.9 Hz), 8.02
(1H, d, J = 7.8 Hz), 8.25 (1H, d, J = 7.9 Hz), 10.50 (1H, br s);
13C NMR (100 MHz, CDCl3) δ 38.7 (q), 45.8 (t), 72.4 (d), 78.1 (s),
106.5 (d), 120.0 (d), 121.6 (d), 128.8 (s), 130.3 (d), 131.3 (s), 131.6
(s), 133.3 (s), 161.8 (s); MS m/z 257 (Mþ). Anal. Calcd for
C13H11N3O3: C, 60.70; H, 4.30; N, 16.33. Found: C, 60.92; H,
4.12; N, 16.21.
Conclusions
In summary, we have developed effective Pd-catalyzed
protocols for the intramolecular carboamination or hydro-
amination reactions of indole allenamides that proceeded
differently giving either R-styryl or simply vinyl imidazo[1,5-
a]indoles. Two remarkable features are worth showing: (i)
the nucleophilic activity of the indole nitrogen in the well-
established carboamination reactions and (ii) the feasibility
of the unusual Pd-catalyzed hydroamination of allenes in
mild conditions under microvawes irradiation. We are cur-
rently working toward the development of a more general
scope of the microwave-assisted hydroamination of allenes.
Experimental Section
General. Melting points are uncorrected. IR spectra were
1
recorded on a FT-IR spectrometer. H NMR and 13C NMR
spectra were recorded at 400 and 100 MHz, respectively. Chem-
ical shifts (δ) are given as ppm relative to the residual solvent
peak (chloroform-d1 7.25 ppm/77 ppm). Mass spectra were
determined with an HPLC-MS apparatus. Elemental analyses
were executed on CHN apparatus analyzer. Column chroma-
tography was performed on silica gel 60 (mesh size 63-200 μm).
The microwave reactions were performed in a standard CEM
Discover instrument with temperature control, using the instru-
ment’s in-built IR sensor.
General Procedure for the Preparation of Propargylamides.
A solution of indole-2-carboxylic acid (6.20 mmol), DMF
(0.3 mL), and oxalyl chloride (18.60 mmol) in anhydrous
CH2Cl2 (40 mL) was stirred at rt for 1 h and refluxed for 1 h.
The solvent was evaporated under reduced pressure, the crude
residue was diluted with CH2Cl2 (40 mL), and a solution of
propargylamine (8.24 mmol) and triethylamine (8.24 mmol) in
CH2Cl2 was added at 0 °C. The solution was stirred at rt for 1 h,
the organic phase was washed with 1 M HCl and dried over
Na2SO4, then the solvent was evaporated under reduced pres-
sure. The resulting crude mixture was purified by flash chroma-
tography to afford the desired product (eluent: light petroleum/
AcOEt 7:3).
N-Benzyl-N-propargyl-1H-indole-2-carboxamide: yield 59%,
white solid, mp 163 °C (i-Pr2O); IR 3313, 3220, 2116, 1668 cm-1
;
1H NMR (400 MHz, CDCl3) δ: 2.37 (1H, s), 4.39 (2H, s), 5.05
(2H, s), 7.09-7.14 (1H, m), 7.15-7.45 (8H, m), 7.63-7.66 (1H,
m), 9.35 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 30.9 (t), 52.8
(t), 74.1 (d), 78.6 (s), 105.7 (d), 111.7 (d), 120.6 (d), 122.2 (d),
122.4 (d), 124.6 (d), 127.7 (s), 127.8 (d), 128.6 (s), 128.8 (d), 135.8
(s), 136.0 (s), 159.0 (s); MS m/z 288 (Mþ). Anal. Calcd for
C19H16N2O: C, 79.14; H, 5.59; N, 9.72. Found: C, 79.22; H, 5.41;
N, 9.65.
N-Methyl-N-propargyl-1H-indole-2-carboxamide (1): yield
96%, white solid, mp 145 °C (i-Pr2O); IR 3308, 3230, 2116,
N-(4-Methoxybenzyl)-N-propargyl-1H-indole-2-carboxamide:
yield 98%, white solid, mp 138 °C (i-Pr2O); IR 3321, 3218, 2108,
1667 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.37 (1H, s), 3.83 (3H,
s), 4.37 (2H, s), 5.00 (2H, s), 6.91-6.94 (2H, m), 7.11-7.15 (1H,
m), 7.27-7.33 (4H, m), 7.44-46 (1H, m), 7.63-7.65 (1H, m),
9.53 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 30.9 (t), 53.4 (t),
55.3 (q), 73.4 (d), 78.7 (s), 105.7 (d), 106.5 (d), 111.8 (d), 114.3 (d),
120.6 (d), 122.2 (d), 124.7 (d), 127.7 (s), 127.9 (s), 128.7 (s), 135.9
(s), 159.3 (s), 163.3 (s); MS m/z 318 (Mþ). Anal. Calcd for
1
1661 cm-1; H NMR (400 MHz, CDCl3) δ 2.37 (1H, s), 3.23
(3H, s), 4.49 (2H, s), 7.00 (1H, s), 7.15 (1H, dd, J = 8.0 Hz, 7.1
Hz), 7.30 (1H, dd, J = 8.2 Hz, 7.1 Hz), 7.46 (1H, d, J = 8.2 Hz),
7.69 (1H, d, J = 8.0 Hz), 9.56 (1H, br s); 13C NMR (100 MHz,
CDCl3) δ 35.8 (q), 40.3 (t), 73.2 (d), 78.5 (s), 106.4 (d), 112.3 (d),
120.7 (d), 122.3 (d), 124.8 (d), 127.8 (s), 129.0 (s), 136.3 (s), 163.6
(s); MS m/z 212 (Mþ). Anal. Calcd for C13H12N2O: C, 73.57; H,
5.70; N, 13.20. Found: C, 73.41; H, 5.82; N, 13.34.
6928 J. Org. Chem. Vol. 75, No. 20, 2010

Beccalli et al.
JOCArticle
14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.34; H,
C20H18N2O2: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.38; H,
5.85; N, 8.92.
C
5.89; N, 11.49.
N-(4-Methylbenzyl)-N-propargyl-1H-indole-2-carboxamide:
yield 98%, white solid, mp 138 °C (i-Pr2O); IR 3309, 3222,
2120, 1670 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.38 (4H, s),
4.36 (2H, s), 5.01 (2H, s), 7.11-7.65 (9H, m), 9.26 (1H, br s);
13C NMR (100 MHz, CDCl3) δ 21.1 (q), 33.9 (t), 49.1 (t), 72.8
(d), 78.7 (s), 105.7 (d), 106.5 (d), 111.8 (d), 120.6 (d), 122.1
(d), 124.7 (d), 127.6 (s), 128.6 (s), 129.6 (d), 132.9 (s), 135.9 (s),
137.6 (s), 163.4 (s); MS m/z 302 (Mþ). Anal. Calcd for
C20H18N2O: C, 79.44; H, 6.00; N, 9.26. Found: C, 79.52; H,
5.87; N, 9.21.
N-(4-Chlorobenzyl)-N-propargyl-1H-indole-2-carboxamide:
yield 58%, white solid, mp 166 °C (i-Pr2O); IR 3320, 3210,
2109, 1657 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.41 (1H, s),
4.42 (2H, s), 5.02 (2H, s), 7.12-7.65 (9H, m), 10.06 (1H, br s);
13C NMR (100 MHz, CDCl3) δ 34.1 (t), 50.3 (t), 73.3 (d), 78.5
(s), 105.8 (d), 105.9 (d), 112.0 (d), 120.6 (d), 122.1 (d), 124.8 (d),
127.5 (s), 128.3 (s), 129.1 (d), 133.7 (s), 134.7 (s), 136.2 (s), 163.6
(s); MS m/z 322 (Mþ). Anal. Calcd for C19H15ClN2O: C, 70.70;
H, 4.68; N, 8.68. Found: C, 70.88; H, 4.53; N, 8.49.
N-Propargyl-N-(thiophen-2-ylmethyl)-1H-indole-2-carboxamide:
yield 51%, white solid, mp 121 °C (i-Pr2O); IR 3312, 3220, 2114,
1676 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.44 (1H, s), 4.46 (2H,
s), 5.15 (2H, s), 7.00-7.03 (1H, m), 7.09-7.17 (3H, m), 7.27-7.32
(2H, m), 7.48 (1H, d, J = 8.3 Hz), 7.68 (1H, d, J = 8.0 Hz), 9.87
(1H, brs);13CNMR(100MHz, CDCl3) δ37.6 (t), 44.4 (t), 73.2 (d),
78.6 (s), 105.8 (d), 112.0 (d), 122.2 (d), 124.8 (d), 126.1 (d), 126.9 (d),
127.0 (d), 127.1 (d), 127.6 (s), 128.4 (s), 136.1 (s), 138.4 (s), 163.2 (s);
MS m/z 294 (Mþ). Anal. Calcd for C17H14N2OS: C, 69.36; H, 4.79;
N, 9.52. Found: C, 69.55; H, 4.91; N, 9.63.
Synthesis of Allenamides 2, 8, and 15a-i. A solution of
propargylamide (1 mmol) in THF (10 mL) was treated with
t-BuOK (2.5 mmol). The resulting solution was stirred at rt for
1 min, then filtered on silica gel (AcOEt). The solvent was evapo-
rated under reduced pressure and the residue was used without
further purification for the next step.
N-Methyl-N-(propa-1,2-dienyl)-1H-indole-2-carboxamide (2):
yield 98%, white solid, mp 143 °C (i-Pr2O); IR 3306, 1940, 1668
cm-1; 1H NMR (400 MHz, CDCl3) δ 3.34 (3H, s), 4.49 (2H, d,
J = 6.6 Hz), 7.00 (1H, s), 7.17 (1H, dd, J = 8.2 Hz, 7.0 Hz),
7.27-7.72 (1H, m), 7.28 (1H, dd, J = 8.8 Hz, 7.0 Hz), 7.44 (1H,
d, J = 8.2 Hz), 7.68 (1H, d, J = 8.8 Hz), 9.07 (1H, br s);
13C NMR (100 MHz, CDCl3) δ 33.7 (q), 87.6 (t), 102.7 (d), 107.9
(d), 112.0 (d), 120.9 (d), 122.4 (d), 125.2 (d), 127.9 (s), 129.1 (s),
136.1 (s), 161.7 (s), 202.4 (s); MS m/z 212 (Mþ). Anal. Calcd for
C13H12N2O: C, 73.57; H, 5.70; N, 13.20. Found: C, 73.43; H,
5.79; N, 13.11.
N-(2-Iodobenzyl)-N-(propa-1,2-dienyl)-1H-indole-2-carboxa-
mide (8): yield 98%, white solid, mp 171 °C (i-Pr2O); IR 3296,
1949, 1650 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.96 (2H, s),
5.29 (2H, d, J = 6.2 Hz), 7.12-7.34 (6H, m), 7.40 (1H, s),
7.45-7.67 (2H, m), 7.87-7.96 (1H, m), 9.02 (1H, br s); 13C
NMR (100 MHz, CDCl3) δ 45.7 (t), 85.2 (t), 96.1 (s), 110.0 (d),
111.1 (d), 114.9 (d), 119.8 (d), 120.7 (d), 121.7 (d), 127.4 (d),
128.3 (d), 128.5 (d), 131.3 (s), 138.5 (s), 139.1 (d), 139.8 (s), 151.3
(s), 162.8 (s), 204.5 (s); MS m/z 414 (Mþ). Anal. Calcd for
C19H15IN2O: C, 55.09; H, 3.65; N, 6.76. Found: C, 54.88; H,
3.76; N, 6.77.
N-Methyl-N-(propa-1,2-dienyl)-5-methyl-1H-indole-2-car-
boxamide (15b): yield 88%. white solid. mp 135 °C (i-Pr2O);
IR 3301, 1944, 1660 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.46
(3H, s), 3.36 (3H, s), 5.51 (2H, d, J = 6.3 Hz), 6.92 (1H, s), 7.13
(1H, d, J = 8.4 Hz), 7.36 (1H, d, J = 8.4 Hz), 7.45 (1H, s),
7.50-7.79 (1H, m), 9.80 (1H, br s); 13C NMR (100 MHz,
CDCl3) δ 21.4 (q), 30.3 (q), 87.3 (t), 106.8 (d), 111.6 (d), 121.4
(d), 121.9 (d), 126.8 (d), 127.8 (s), 128.9 (s), 129.9 (s), 134.6 (s),
162.0 (s), 202.5 (s); MS m/z 226 (Mþ). Anal. Calcd for
C14H14N2O: C, 74.31; H, 6.24; N, 12.38. Found: C, 74.14;
H, 6.35; N, 12.22.
N-Methyl-N-(propa-1,2-dienyl)-5-chloro-1H-indole-2-car-
boxamide (15c): yield 85%, white solid, mp 145 °C (i-Pr2O);
IR 3313, 1937, 1655 cm-1 1H NMR (400 MHz, CDCl3)
;
δ 3.31 (3H, s), 5.52 (2H, d, J = 6.3 Hz), 6.92 (1H, s), 7.25 (1H,
d, J = 8.8 Hz), 7.39 (1H, d, J = 8.8 Hz), 7.64 (1H, s), 7.23-7.82
(1H, m), 10.16 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 32.8 (q),
87.5 (t), 106.6 (d), 113.1 (d), 121.2 (d), 121.8 (d), 125.3 (d), 126.2
(s), 128.4 (s), 130.1 (s), 134.5 (s), 161.4 (s), 201.8 (s); MS m/z 246
(Mþ). Anal. Calcd for C13H11ClN2O: C, 63.29; H, 4.49; N, 11.36.
Found: C, 63.44; H, 4.23; N, 11.23.
N-Methyl-N-(propa-1,2-dienyl)-7-nitro-1H-indole-2-carboxa-
mide (15d): yield 80%, white solid, mp 128 °C (i-Pr2O); IR 3302,
1945, 1667 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.27 (3H, s),
5.51 (2H, d, J = 6.3 Hz), 6.97 (1H, s), 7.27 (1H, dd, J = 7.4 Hz,
7.8 Hz), 7.32-7.47 (1H, m), 8.02 (1H, d, J = 7.8 Hz), 8.25 (1H,
d, J = 7.4 Hz), 10.50 (1H, br s); 13C NMR (100 MHz, CDCl3) δ
30.3 (q), 87.6 (t), 107.6 (d), 119.9 (d), 121.7 (d), 122.1 (d), 128.9
(s), 130.3 (d), 131.1 (s), 131.6 (s), 133.3 (s), 160.1 (s), 202.0 (s);
MS m/z 257 (Mþ). Anal. Calcd for C13H11N3O3: C, 60.70; H,
4.30; N, 16.33. Found: C, 60.51; H, 4.54; N, 16.42.
N-Benzyl-N-(propa-1,2-dienyl)-1H-indole-2-carboxamide (15e):
yield 69%, white solid, mp 145 °C (i-Pr2O); IR 3298, 1953, 1669
cm-1; 1H NMR (400 MHz, CDCl3) δ 5.01 (2H, s), 5.36 (2H, s),
7.11-7.68 (11H, m), 9.34 (1H, br s); 13C NMR(100 MHz, CDCl3)
δ 49.8 (t), 87.5 (t), 102.6 (d), 107.5 (d), 111.7 (d), 120.7 (d), 122.3
(d), 125.0 (d), 127.2 (d), 127.6 (d), 127.8 (s), 128.4 (s), 128.6 (d),
136.0 (s), 137.2 (s), 161.6 (s), 202.8 (s); MS m/z 288 (Mþ). Anal.
Calcd for C19H16N2O: C, 79.14; H, 5.59; N, 9.72. Found: C, 78.98;
H, 5.62; N, 9.88.
N-(4-Methoxybenzyl)-N-(propa-1,2-dienyl)-1H-indole-2-car-
boxamide (15f): yield 84%, white solid, mp 136 °C (i-Pr2O); IR
3310, 1954, 1670 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.81 (3H,
s), 4.90 (2H, s), 5.39 (2H, s), 6.88-7.43 (10H, m), 9.41 (1H, br s);
13C NMR (100 MHz, CDCl3) δ 47.4 (t), 55.3 (q), 87.4 (t), 102.1
(d), 108.2 (d), 111.8 (d), 114.0 (d), 120.7 (d), 122.3 (d), 125.0 (d),
127.6 (s), 128.7 (s), 129.2 (s), 130.0 (d), 136.0 (s), 158.8 (s), 161.5
(s), 202.4 (s); MS m/z 318 (Mþ). Anal. Calcd for C20H18N2O2:
C, 75.45; H, 5.70; N, 8.80. Found: C, 75.51; H, 5.62; N, 8.72.
N-(4-Methylbenzyl)-N-(propa-1,2-dienyl)-1H-indole-2-car-
boxamide (15g): yield 92%, white solid, mp 155 °C (i-Pr2O);
IR 3310, 1933, 1655 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.36
(3H, s), 4.90 (2H, s), 5.38 (2H, s), 7.03-7.77 (10H, m), 9.62
(1H, br s); 13C NMR (100 MHz, CDCl3) δ 21.4 (q), 43.2 (t),
87.2 (t), 102.3 (d), 108.0 (d), 111.7 (d), 114.1 (d), 120.9 (d),
122.5 (d), 125.3 (d), 127.3 (s), 128.6 (d), 131.4 (s), 133.0 (s),
136.1 (s), 136.9 (s), 161.7 (s), 202.6 (s); MS m/z 302 (Mþ). Anal.
Calcd for C20H18N2O: C, 79.44; H, 6.00; N, 9.26. Found: C,
79.55; H, 5.81; N, 9.31.
N-Methyl-N-(propa-1,2-dienyl)-5-methoxy-1H-indole-2-car-
boxamide (15a): yield 85%, white solid, mp 143 °C (i-Pr2O); IR
1
3310, 1935, 1672 cm-1; H NMR (400 MHz, CDCl3) δ 3.35
N-(4-Chlorobenzyl)-N-(propa-1,2-dienyl)-1H-indole-2-car-
boxamide (15h): yield 92%, white solid, mp 167 °C (i-Pr2O);
IR 3295, 1938, 1652 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.96
(2H, s), 5.37 (2H, d, J = 5.9 Hz), 6.85-7.64 (10H, m), 9.28
(1H, br s); 13C NMR (100 MHz, CDCl3) δ 48.6 (t), 87.7 (t),
101.9 (d), 108.0 (d), 111.8 (d), 120.8 (d), 122.3 (d), 125.1 (d),
127.5 (d), 127.5 (s), 128.8 (d), 129.9 (s), 133.1 (s), 135.7 (s),
(3H, s), 3.86 (3H, s), 5.50 (2H, d, J = 6.3 Hz), 6.92 (1H, s), 6.99
(1H, d, J = 8.9 Hz), 7.08 (1H, s), 7.36 (1H, d, J = 8.9 Hz),
7.57-7.88 (1H, m), 9.22 (1H, br s); 13C NMR (100 MHz,
CDCl3) δ 33.2 (q), 55.7 (q), 87.4 (t), 102.3 (d), 102.6 (d),
106.9 (d), 112.8 (d), 116.3 (d), 127.9 (s), 129.3 (s), 131.6 (s),
154.6 (s), 161.6 (s), 201.9 (s); MS m/z 242 (Mþ). Anal. Calcd for
J. Org. Chem. Vol. 75, No. 20, 2010 6929

Beccalli et al.
JOCArticle
136.1 (s), 161.6 (s), 202.1 (s); MS m/z 322 (Mþ). Anal. Calcd
for C19H15ClN2O: C, 70.70; H, 4.68; N, 8.68. Found: C,
70.65; H, 4.81; N, 8.94.
(Mþ). Anal. Calcd for C22H20N2O3: C, 73.32; H, 5.59; N, 7.77.
Found: C, 73.14; H, 5.71; N, 7.89.
2-Methyl-3-(1-(4-nitrophenyl)vinyl)-2,3-dihydro-1H-imidazo-
[1,5-a]indol-1-one (5e): yield 68%, white solid, mp 190 °C
N-(Propa-1,2-dienyl)-N-(thiophen-2-ylmethyl)-1H-indole-2-car-
boxamide (15i): yield 95%, white solid, mp 166 °C (i-Pr2O); IR
3321, 1952, 1654 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.10 (2H,
s), 5.54 (2H, d, J = 5.3 Hz), 6.95-7.45 (1H, m), 6.96-6.99 (1H,
m), 7.06-7.17 (3H, m), 7.24-7.27 (1H, m), 7.31 (1H, dd, J = 7.6
Hz, 7.7 Hz), 7.43 (1H, d, J = 8.3 Hz), 7.67 (1H, d, J = 8.0 Hz),
9.47 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 45.5 (t), 88.1 (t),
101.8 (d), 107.7 (d), 111.8 (d), 120.8 (d), 122.3 (d), 125.1 (d), 125.5
(d), 126.5 (d), 127.5 (d), 128.5 (s), 130.3 (s), 136.1 (s), 139.8 (s),
161.2 (s), 201.9 (s); MS m/z 294 (Mþ). Anal. Calcd for
C17H14N2OS: C, 69.36; H, 4.79; N, 9.52. Found: C, 69.21; H,
4.85; N, 9.44.
(i-Pr2O); IR 1654 cm-1; H NMR (400 MHz, CDCl3) δ 3.03
1
(3H, s), 5.94 (1H, s), 6.07 (1H, s), 6.09 (1H, s), 6.84 (2H, d, J =
8.7 Hz), 6.89 (1H, s), 7.18 (1H, dd, J = 8.0 Hz, 7.1 Hz), 7.27 (1H,
dd, J = 8.2 Hz, 7.1 Hz), 7.33 (1H, d, J = 8.1 Hz), 7.73 (1H, d,
J = 8.0 Hz), 7.93 (2H, d, J = 8.7 Hz); 13C NMR (100 MHz,
CDCl3) δ 26.9 (q), 76.9 (d), 98.6 (d), 109.9 (d), 121.4 (d), 123.7
(d), 123.9 (d), 124.5 (d), 125.9 (t), 127.9 (d), 131.3 (s), 131.9 (s),
132.8 (s), 142.0 (s), 142.5 (s), 147.8 (s), 160.6 (s); MS m/z 333
(Mþ). Anal. Calcd for C19H15N3O3: C, 68.46; H, 4.54; N, 12.61.
Found: C, 68.12; H, 4.65; N, 12.50.
Synthesis of Imidazo[1,5-a]indoles Derivatives 7a-d. Pd(PPh3)4
(8%), aryl iodide (1.5 mmol), and K2CO3 (4 mmol) were added
to a solution of 2 (1 mmol) in acetonitrile (10 mL) under
CO atmosphere (balloon). The resulting suspension was stirred
at rt for 48 h. The solvent was evaporated under reduced pressure,
then the crude mixture was diluted with brine and extracted with
AcOEt (3 ꢀ 20 mL). The organic phase was dried over Na2SO4
and the product was purified by flash chromatography.
Synthesis of Imidazo[1,5-a]indoles Derivatives 5a-e. K2CO3
(4 mmol), aryl iodide (1.5 mmol), and Pd(PPh3)4 (5 mol %) were
added to a solution of allenamide (1 mmol) in acetonitrile
(10 mL). The resulting solution was heated at reflux for 2 h.
The solvent was evaporated under reduced pressure, then the
resulting crude mixture was diluted with brine and extracted
with AcOEt (3 ꢀ 20 mL). The organic phase was dried over
Na2SO4 and the product was purified by flash chromatography.
2-Methyl-3-(1-phenylvinyl)-2,3-dihydro-1H-imidazo[1,5-a]indol-
1-one (5a): yield 74%, white solid, mp 178 °C (i-Pr2O); IR 1670
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.99 (3H, s), 5.82 (1H, s),
5.86 (1H, s), 6.01 (1H, s), 6.73 (2H, d, J = 7.4 Hz), 6.90 (1H, s),
7.10 (2H, dd, J = 7.7 Hz, 7.2 Hz), 7.16-7.19 (2H, m), 7.24-7.27
2-Methyl-3-(3-oxo-3-phenylprop-1-en-2-yl)-2,3-dihydro-1H-
imidazo[1,5-a]indol-1-one (7a): yield 45%, white solid, mp
133 °C (i-Pr2O); IR 1730, 1640 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 3.10 (3H, s), 5.88 (1H, s), 6.10 (1H, s), 6.57 (1H, s),
6.97 (1H, s), 7.10-7.27 (3H, m), 7.45-7.51 (2H, m), 7.60-7.64
(1H, m), 7.74-7.81 (3H, m); 13C NMR (100 MHz, CDCl3) δ
27.5 (q), 70.5 (d), 98.3 (d), 110.3 (d), 121.1 (d), 123.7 (d), 124.2
(d), 128.7 (d), 129.6 (d), 131.2 (t), 131.7 (s), 132.0 (s), 132.5 (s),
133.5 (d), 136.1 (s), 142.0 (s), 160.7 (s), 195.3 (s); MS m/z 316
(Mþ). Anal. Calcd for C20H16N2O2: C, 75.93; H, 5.10; N, 8.85.
Found: C, 75.87; H, 5.22; N, 8.72.
(1H, m), 7.34 (1H, d, J = 8.2 Hz), 7.76 (1H, d, J = 8.0 Hz); 13
C
NMR (100 MHz, CDCl3) δ 27.1 (q), 77.5 (d), 98.3 (d), 110.5 (d),
121.3 (d), 123.6 (t), 123.8 (d), 124.2 (d), 127.1 (d), 128.8 (d), 128.9
(d), 132.0 (s), 132.1 (s), 133.2 (s), 135.9 (s), 144.2 (s), 161.0 (s); MS
m/z 288 (Mþ). Anal. Calcd for C19H16N2O: C, 79.14; H, 5.59; N,
9.71. Found: C, 79.33; H, 5.45; N, 9.50.
3-(1-(4-Methoxyphenyl)vinyl)-2-methyl-2,3-dihydro-1H-imidazo-
[1,5-a]indol-1-one (5b): yield 88%, white solid, mp 140 °C (i-Pr2O);
IR 1666 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.99 (3H, s), 3.68
(3H, s), 5.77 (1H, s), 5.80 (1H, s), 6.03 (1H, s), 6.62-6.79 (4H, m),
6.91 (1H, s), 7.17 (1H, dd, J= 8.0 Hz, 7.6 Hz), 7.25 (1H, dd, J=8.2
Hz, 7.6 Hz), 7.35 (1H, d, J = 8.2 Hz), 7.74 (1H, d, J = 8.0 Hz);
13C NMR (100 MHz, CDCl3) δ 26.8 (q), 55.1 (q), 77.4 (d), 97.9 (d),
110.3 (d), 114.0 (d), 121.0 (d), 122.3 (t), 123.6 (d), 123.9 (d), 127.8
(s), 128.0 (d), 128.6 (s), 131.8 (s), 133.0 (s), 143.3 (s), 159.8 (s), 160.8
(s); MS m/z 318 (Mþ). Anal. Calcd for C20H18N2O2: C, 75.45; H,
5.70; N, 8.80. Found: C, 75.17; H, 5.98; N, 9.01.
3-(3-(4-Methoxyphenyl)-3-oxoprop-1-en-2-yl)-2-methyl-2,3-
dihydro-1H-imidazo[1,5-a]indol-1-one (7b): yield 31%, white
solid, mp 163 °C (i-Pr2O); IR 1724, 1633 cm-1; 1H NMR (400
MHz, CDCl3) δ 3.10 (3H, s), 3.89 (3H, s), 5.78 (1H, s), 6.03 (1H,
s), 6.56 (1H, s), 6.96 (2H, d, J = 9.0 Hz), 6.97 (1H, s), 7.17-7.23
(3H, m), 7.76 (1H, d, J = 7.8 Hz), 7.84 (2H, d, J = 9.0 Hz); 13
C
NMR (100 MHz, CDCl3) δ 27.5 (q), 55.6 (q), 70.8 (d), 98.3 (d),
110.0 (s), 110.4 (d), 114.0 (d), 121.1 (d), 123.7 (d), 124.1 (d),
128.6 (s), 129.2 (t), 131.9 (s), 132.2 (d), 132.5 (s), 142.2 (s), 164.1
(s), 193.7 (s), 206.9 (s); MS m/z 346 (Mþ). Anal. Calcd for
C
5.34; N, 8.18.
21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C, 72.67; H,
3-(1-(4-Acetylphenyl)vinyl)-2-methyl-2,3-dihydro-1H-imidazo-
[1,5-a]indol-1-one (5c): yield 76%, yellow oil; IR 1652 cm-1; 1H
NMR (400MHz, CDCl3) δ 2.44(3H, s), 2.97 (3H, s), 5.88(1H, s),
5.97 (1H, s), 5.99 (1H, s), 6.76 (2H, d, J = 8.6 Hz), 6.88 (1H, s),
7.16 (1H, dd, J = 6.9 Hz, 8.1 Hz), 7.23 (1H, dd, J = 6.9 Hz, 8.2
Hz), 7.29 (1H, d, J = 8.2 Hz), 7.71 (1H, d, J = 8.1 Hz), 7.71 (2H,
d, J = 8.6 Hz); 13C NMR (100 MHz, CDCl3) δ 26.5 (q), 26.9 (q),
76.8 (d), 98.3 (d), 110.1 (d), 121.3 (d), 123.7 (d), 124.2 (d), 124.9
(t), 127.1 (d), 128.5 (d), 131.5 (s), 131.8 (s), 132.9 (s), 136.8 (s),
140.2 (s), 143.1 (s), 160.7 (s), 197.4 (s); MS m/z 330 (Mþ). Anal.
Calcd for C21H18N2O2: C, 76.34; H, 5.49; N, 8.48. Found: C,
76.55; H, 5.16; N, 8.52.
3-(3-(4-Acetylphenyl)-3-oxoprop-1-en-2-yl)-2-methyl-2,3-di-
hydro-1H-imidazo[1,5-a]indol-1-one (7c): yield 28%, white
solid, mp 145 °C (i-Pr2O); IR 1738, 1636 cm-1 1H NMR
;
(400 MHz, CDCl3) δ 2.66 (3H, s), 3.12 (3H, s), 5.96 (1H, s),
6.12 (1H, s), 6.60 (1H, s), 6.99 (1H, s), 7.18-7.27 (3H, m), 7.77
(1H, d, J = 8.0 Hz), 7.85 (2H, d, J = 8.4 Hz), 8.04 (2H, d, J =
8.4 Hz); 13C NMR (100 MHz, CDCl3) δ 26.8 (q), 27.5 (q), 70.4
(d), 98.5 (d), 110.1 (d), 121.2 (d), 123.8 (d), 124.3 (d), 128.5 (d),
129.7 (d), 131.6 (s), 132.0 (t), 132.4 (s), 135.0 (s), 139.6 (s), 140.4
(s), 142.1 (s), 160.6 (s), 194.7 (s), 197.1 (s); MS m/z 358 (Mþ).
Anal. Calcd for C22H18N2O3: C, 73.73; H, 5.06; N, 7.82.
Found: C, 73.84; H, 4.95; N, 7.92.
2-Methyl-3-(1-(4-ethoxycarbonylphenyl)vinyl)-2,3-dihydro-
1H-imidazo[1,5-a]indol-1-one (5d): yield 72%, yellow oil; IR
1659 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.30 (3H, t, J = 7.1
Hz), 2.97 (3H, s), 4.27 (2H, q, J = 7.1 Hz), 5.85 (1H, s), 5.92
(1H, s), 5.95 (1H, s), 6.75 (2H, d, J = 8.5 Hz), 6.87 (1H, s), 7.16
(1H, dd, J = 6.9 Hz, 8.0 Hz), 7.23 (1H, dd, J = 6.9 Hz, 8.2 Hz),
7.29 (1H, d, J = 8.2 Hz), 7.71 (1H, d, J = 8.0 Hz), 7.76 (2H, d,
J = 8.5 Hz); 13C NMR (100 MHz, CDCl3) δ 14.2 (q), 26.8 (q),
61.0 (t), 76.9 (d), 98.2 (d), 110.1 (d), 121.2 (d), 123.6 (d), 124.2
(d), 124.7 (t), 126.9 (d), 129.7 (d), 130.5 (s), 131.6 (s), 131.8 (s),
132.9 (s), 140.0 (s), 143.2 (s), 160.6 (s), 165.9 (s); MS m/z 360
3-[3-(4-Ethoxycarbonylphenyl)-3-oxoprop-1-en-2-yl]-2-methyl-
2,3-dihydro-1H-imidazo[1,5-a]indol-1-one (7d): yield 33%, white
1
solid, mp 121 °C (i-Pr2O); IR 1732, 1655 cm-1; H NMR (400
MHz, CDCl3) δ 1.33 (3H, t, J = 7.1 Hz), 3.03 (3H, s), 4.30 (2H, q,
J = 7.1 Hz), 5.90 (1H, s), 5.99 (1H, s), 6.12 (1H, s), 6.80 (2H, d,
J = 8.4 Hz), 6.91 (1H, s), 7.18 (1H, dd, J = 7.0 Hz, 8.0 Hz), 7.27
(1H, dd, J = 7.0 Hz, 8.1 Hz), 7.35 (1H, d, J = 8.0 Hz), 7.74 (1H,
d, J = 8.1 Hz), 7.79 (2H, d, J = 8.4 Hz); 13C NMR (100 MHz,
CDCl3) δ 14.2 (q), 26.9 (q), 61.0 (t), 77.1 (d), 98.4 (d), 110.1 (d),
121.2 (d), 123.7 (d), 124.2 (d), 124.5 (t), 126.9 (d), 129.7 (s), 129.8
(d), 130.6 (s), 131.6 (s), 131.9 (s), 132.9 (s), 140.0 (s), 143.4 (s),
6930 J. Org. Chem. Vol. 75, No. 20, 2010

Beccalli et al.
JOCArticle
160.7 (s), 165.9 (s); MS m/z 388 (Mþ). Anal. Calcd for
C23H20N2O4: C, 71.12; H, 5.19; N, 7.21. Found: C, 71.05; H,
5.32; N, 7.32.
toluene (10 mL) was heated at 150 °C for 1 h under microwave
irradiation, then filtered on a Celite layer. The solvent was
evaporated under reduced pressure and the crude residue was
purified by flash chromatography.
Synthesis of 6-Methylene-6,11-dihydro-5aH-indolo[10,20:3,4]-
imidazo[1,2-b]isoquinolin-13-one (10). K2CO3 (4 mmol) and
Pd(PPh3)4 (5 mol %) were added to a solution of 8 (1 mmol)
in acetonitrile (10 mL). The resulting solution was heated at
reflux for 2 h. The solvent was evaporated under reduced
pressure, then the resulting crude mixture was diluted with brine
and extracted with AcOEt (3 ꢀ 20 mL). The organic phase was
dried over Na2SO4 and the product was purified by flash
chromatography. Yield 80%, white solid, mp 179 °C (i-Pr2O);
IR 1652 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.65 (1H, d, J =
17.6 Hz), 5.24 (1H, s), 5.37 (1H, d, J = 17.6 Hz), 5.61 (1H, s),
6.00 (1H, s), 7.02 (1H, s), 7.22-7.30 (2H, m), 7.33-7.44 (3H, m),
7.47 (1H, d, J = 8.3 Hz), 7.62 (1H, d, J = 7.6 Hz), 7.80 (1H, d,
J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 42.7 (t), 69.4 (d),
98.8 (d), 110.9 (t), 111.0 (d), 121.2 (d), 123.7 (d), 124.4 (d), 126.1
(d), 126.6 (d), 127.8 (d), 129.4 (d), 130.9 (s), 131.1 (s), 131.8 (s),
132.3 (s), 134.3 (s), 139.2 (s), 159.3 (s); MS m/z 286 (Mþ). Anal.
Calcd for C19H14N2O: C, 79.70; H, 4.93; N, 9.78. Found: C,
79.55; H, 5.09; N, 9.89.
2-Methyl-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-1-one (13):
yield 71%, colorless oil; IR 1645 cm-1; H NMR (400 MHz,
1
CDCl3) δ 3.07 (3H, s), 5.30-5.77 (3H, m), 5.88-5.96 (1H, m), 6.92
(1H, s), 7.10 (1H, dd, J = 7.8 Hz, 7.0 Hz), 7.25-7.32 (2H, m), 7.75
(1H, d, J = 8.1 Hz); 13C NMR (100 MHz, CDCl3) δ 26.8 (q), 75.2
(d), 97.9 (d), 110.1 (d), 121.0 (d), 123.6 (d), 123.8 (d), 124.4 (t),
131.4 (s), 131.9 (s), 133.0 (s), 133.5 (d), 160.5 (s); MS m/z 212 (Mþ).
Anal. Calcd for C13H12N2O: C, 73.56; H, 5.70; N, 13.20. Found: C,
73.50; H, 5.85; N, 13.41.
7-Methoxy-2-methyl-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-
1-one (16a): yield 67%, white solid, mp 138 °C (i-Pr2O); IR 1638
cm-1; 1H NMR (400 MHz, CDCl3) δ 3.03 (3H, s), 3.83 (3H, s),
5.59-5.73 (3H, m), 5.85-5.89 (1H, m), 6.80 (1H, s), 6.91 (1H, dd,
J = 8.9 Hz, 2.3 Hz), 7.13 (1H, d, J = 2.3 Hz), 7.16 (1H, d, J = 8.9
Hz); 13C NMR (100 MHz, CDCl3) δ26.7 (q), 55.7 (q), 75.1 (d), 97.3
(d), 103.9 (d), 110.8 (d), 115.1 (d), 124.3 (t), 128.4 (s), 131.9 (s), 132.3
(s), 133.6 (d), 154.8 (s), 160.5 (s); MS m/z 242 (Mþ). Anal. Calcd for
C14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.29; H, 5.99;
N, 11.45.
Synthesis of 2-(2-Iodobenzyl)-4-methylpyrazino[1,2-a]indol-
1(2H)-one (11) (path a). K2CO3 (4 mmol) and Pd(PPh3)4
(5 mol %) were added to a solution of 8 (1 mmol) in DMF (10
mL). The resulting solution was heated at 100 °C for 2 h. The
solvent was evaporated under reducedpressure, then the resulting
crude mixture was diluted with brine and extracted with Et2O
(3 ꢀ 20 mL). The organic phase was dried over Na2SO4, then the
solvent was evaporated under reduced pressure and the product
was purified by flash chromatography. Yield 60%, white solid,
mp 184 °C (i-Pr2O); IR 1639 cm-1; 1H NMR (400 MHz, CDCl3)
δ 2.68 (3H, s), 5.13 (2H, s), 6.02 (1H, s), 6.99 (1H, d, J = 7.9 Hz),
7.15 (1H, d, J = 7.6 Hz), 7.27-7.37 (3H, m), 7.56 (1H, s),
7.83-7.88 (2H, m), 7.98 (1H, d, J = 8.5 Hz); 13C NMR (100
MHz, CDCl3) δ 18.3 (q), 54.0 (t), 98.4 (s), 104.9 (d), 112.0 (d),
113.9 (d), 119.0 (s), 122.2 (d), 122.8 (d), 124.1 (d), 128.5 (s), 128.6
(s), 128.7 (d), 128.8 (d), 129.5 (d), 134.0 (s), 138.7 (s), 139.7 (d),
156.6 (s); MS m/z 414 (Mþ). Anal. Calcd for C19H15IN2O: C,
55.09; H, 3.65; N, 6.76. Found: C, 55.17; H, 3.52; N, 6.72.
Synthesis of 6-Methyl-11H-isoindolo[20,10:4,5]pyrazino[1,2-a]-
indol-13-one (12) (path b). AcOK (1 mmol), TBAC (1 mmol),
and Pd(OAc)2 (5 mol %) were added to a solution of 11 (1 mmol)
in DMF (10 mL). The resulting solution was heated at 100 °C for
24 h. The solvent was evaporated under reduced pressure, then
the resulting crude mixture was diluted with brine and extracted
with Et2O (3 ꢀ 20 mL). The organic phase was dried over
Na2SO4 and the product was purified by flash chromatography.
Yield 64%, white solid, mp 181 °C (i-Pr2O); IR 1642 cm-1; 1H
NMR (400 MHz, CDCl3) δ 3.18 (3H, s), 5.14 (2H, s), 7.27-7.52
2,7-Dimethyl-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-1-one
(16b): yield 78%, white solid, mp 122 °C (i-Pr2O); IR 1655 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.44 (3H, s), 3.04 (3H, s),
5.60-5.74 (3H, m), 5.85-5.91 (1H, m), 6.82 (1H, s), 7.09 (1H,
d, J = 8.5 Hz), 7.17 (1H, d, J = 8.5 Hz), 7.51 (1H, s); 13C NMR
(100 MHz, CDCl3) δ 21.4 (q), 26.7 (q), 75.1 (d), 97.2 (d), 109.7 (d),
122.9 (d), 124.2 (t), 125.6 (d), 130.3 (s), 131.5 (s), 132.2 (s), 133.2 (s),
133.6 (d), 160.6 (s); MS m/z 226 (Mþ). Anal. Calcd for C14H14N2O:
C, 74.31; H, 6.24; N, 12.38. Found: C, 74.17; H, 6.45; N, 12.50.
7-Chloro-2-methyl-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-
1-one (16c): yield 85%, white solid, mp 144 °C (i-Pr2O); IR 1632
cm-1;1H NMR(400MHz, CDCl3) δ3.04 (3H, s), 5.60-5.93 (4H,
m), 6.79 (1H, s), 7.17 (2H, s), 7.67 (1H, s); 13C NMR (100 MHz,
CDCl3) δ 26.8 (q), 75.1 (d), 97.2 (d), 111.0 (d), 122.6 (d), 124.3 (d),
124.8 (t), 126.6 (s), 131.2 (s), 132.6 (s), 132.7 (s), 133.1 (d), 160.0
(s); MS m/z 246 (Mþ). Anal. Calcd for C13H11ClN2O: C, 63.29;
H, 4.49; N, 11.36. Found: C, 63.41; H, 4.34; N, 11.22.
2-Methyl-5-nitro-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-
1-one (16d): yield 58%, white solid, mp 170 °C (i-Pr2O); IR 1652
1
cm-1; H NMR (400 MHz, CDCl3) δ 3.12 (3H, s), 5.37-5.45
(1H, m), 5.51-5.61 (2H, m), 6.37 (1H, d, J = 7.6 Hz), 7.09 (1H,
s), 7.27 (1H, dd, J = 7.9 Hz, 8.0 Hz), 8.06 (1H, d, J = 7.9 Hz),
8.11 (1H, d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 27.0
(q), 76.8 (d), 99.3 (d), 120.3 (d), 121.6 (d), 124.1 (t), 125.1 (s),
130.7 (d), 133.3 (d), 135.1 (s), 135.2 (s), 136.1 (s), 158.9 (s); MS m/
z 257 (Mþ). Anal. Calcd for C13H11N3O3: C, 60.70; H, 4.31; N,
16.33. Found: C, 60.58; H, 4.44; N, 16.52.
(6H, m), 7.83 (2H, d, J = 7.8 Hz), 8.14 (1H, d, J = 8.6 Hz); 13
C
2-Benzyl-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-1-one (16e):
1
NMR (100 MHz, CDCl3) δ: 16.1 (q), 53.4 (t), 102.2 (s), 114.1 (s),
114.9 (d), 115.6 (d), 119.8 (d), 123.5 (d), 124.3 (d), 126.2 (d),
126.6 (d), 127.2 (s), 127.7 (d), 129.9 (d), 136.7 (s), 143.2 (s), 143.4
(s), 144.5 (s), 151.4 (s); MS m/z 286 (Mþ). Anal. Calcd for
C19H14N2O: C, 79.70; H, 4.93; N, 9.78. Found: C, 79.82; H, 4.79;
N, 9.65.
Synthesis of 6-Methyl-11H-isoindolo[20,10:4,5]pyrazino[1,2-
a]indol-13-one (12) (path c). AcOK (1 mmol), TBAC (1 mmol),
and Pd(OAc)2 (5 mol %) were added to a solution of 8 (1 mmol)
in DMF (10 mL). The resulting solution was heated at 100 °C
for 24 h. The solvent was evaporated under reduced pressure,
then the resulting crude mixture was diluted with brine and
extracted with Et2O (3ꢀ20 mL). The organic phase was dried
over Na2SO4 and the product was purified by flash chromatog-
raphy. Yield 60%.
yield 63%, white solid, mp 111 °C (i-Pr2O); IR 1648 cm-1; H
NMR (400 MHz, CDCl3) δ 4.14 (1H, d, J = 15.2 Hz), 5.35 (1H, d,
J = 15.2 Hz), 5.64-5.77 (4H, m), 6.98 (1H, s), 7.17-7.36 (8H, m),
7.75 (1H, d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 43.6 (t),
72.9 (d), 98.2 (d), 110.1 (d), 121.0 (d), 123.6 (d), 123.9 (d), 124.5 (t),
128.0 (d), 128.3 (d), 128.9 (d), 131.1 (s), 131.9 (s), 133.0 (s), 133.4 (d),
136.2 (s), 160.3 (s); MS m/z 288 (Mþ). Anal. Calcd for C19H16N2O:
C, 79.14; H, 5.59; N, 9.72. Found: C, 79.26; H, 5.48; N, 9.54.
2-(4-Methoxybenzyl)-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-
1-one (16f): yield 89%, white solid, mp 113 °C (i-Pr2O); IR 1659
cm-1; 1H NMR (400 MHz, CDCl3) δ 3.79 (3H, s) 4.08 (1H, d, J =
15.0 Hz), 5.27 (1H, d, J = 15.0 Hz), 5.64-5.73 (4H, m), 6.87-6.89
(2H, m), 6.96 (1H, s), 7.14-7.18 (1H, m), 7.22-7.26 (4H, m), 7.74
(1H, d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 43.1 (t), 55.3
(q), 72.8 (d), 98.1 (d), 110.1 (d), 114.3 (d), 121.0 (d), 123.5 (d), 123.9
(d), 124.5 (t), 128.3 (s), 129.7 d), 131.3 (s), 131.8 (s), 133.0 (s), 133.4
(d), 159.3 (s), 160.3 (s); MS m/z 318 (Mþ). Anal. Calcd for
Synthesis of Vinyl Imidazo[1,5-a]indoles 13 and 16a-h. A
mixture of allenamide (1 mmol) and Pd(PPh3)4 (0.08 mmol) in
J. Org. Chem. Vol. 75, No. 20, 2010 6931

Beccalli et al.
JOCArticle
C20H18N2O2:C,75.45;H,5.70;N,8.80.Found:C,75.38;H,5.61;N,
8.92.
3-(1-Deuteriumvinyl)-2-methyl-2,3-dihydro-1H-imidazo[1,5-a]-
indol-1-one (18): yield 68%, colorless oil; IR 1639 cm-1; 1H NMR
(400 MHz, CDCl3) δ 3.07 (3H, s), 5.70-5.75 (2H, m), 5.89-5.92
2-(4-Methylbenzyl)-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-
1-one (16g): yield 69%, white solid, mp 138 °C (i-Pr2O); IR 1648
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.36 (3H, s), 4.10 (1H, d,
J = 15.1 Hz), 5.32 (1H, d, J = 15.1 Hz), 5.63-5.82 (4H, m), 6.98
(1H, s), 7.15-7.27 (7H, m), 7.74-7.77 (1H, m); 13C NMR (100
MHz, CDCl3) δ21.1(q), 43.4 (t), 72.8 (d), 98.1(d), 110.1(d), 121.0
(d), 123.5 (d), 123.9 (d), 124.5 (t), 128.3 (d), 129.7 (d), 131.2 (s),
131.9 (s), 133.0 (s), 133.2 (s), 133.4 (d), 137.7 (s), 160.3 (s); MS m/z
302 (Mþ). Anal. Calcd for C20H18N2O: C, 79.44; H, 6.00; N, 9.26.
Found: C, 79.58; H, 5.88; N, 9.18.
2-(4-Chlororbenzyl)-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]indol-
1-one (16h): yield 85%,. white solid, mp 131 °C (i-Pr2O); IR 1650
cm-1; 1H NMR (400 MHz, CDCl3) δ 4.16 (1H, d, J = 15.4 Hz),
5.24 (1H, d, J=15.4 Hz), 5.63-5.82 (4H, m), 6.98 (1H, s), 7.16-
7.20 (1H, m), 7.24-7.27 (4H, m), 7.30-7.35 (2H, m), 7.75 (1H,
d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 43.0 (t), 73.0
(d), 98.4 (d), 110.1 (d), 121.1 (d), 123.6 (d), 124.1 (d), 124.7 (t),
129.1 (d), 129.7 (d), 130.8 (s), 131.8 (s), 133.1 (s), 133.3 (d), 133.9 (s),
134.8 (s), 160.3 (s); MS m/z 322 (Mþ). Anal. Calcd for
C19H15ClN2O: C, 70.70; H, 4.68; N, 8.68. Found: C, 70.88; H,
4.51; N, 8.55.
2-(Tiophen-2-ylmethyl)-3-vinyl-2,3-dihydro-1H-imidazo[1,5-a]-
indol-1-one (16i): yield 72%, white solid, mp 112 °C (i-Pr2O); IR
1656 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.38 (1H, d, J = 15.7
Hz), 5.40 (1H, d, J = 15.7 Hz), 5.67-5.90 (1H, d, J = 16.4 Hz),
6.97-6.99 (2H, m), 7.04-7.05 (1H, m), 7.15-7.19 (1H, m),
7.23-7.27 (3H, m), 7.74 (1H, d, J = 8.0 Hz); 13C NMR
(100 MHz, CDCl3) δ 38.0 (t), 72.8 (d), 98.4 (d), 110.1 (d), 121.1
(d), 123.6 (d), 124.0 (d), 124.9 (t), 126.0 (d), 127.1 (d), 127.3 (d),
130.9 (s), 131.8 (s), 133.1 (s), 133.2 (d), 138.5 (s), 159.9 (s); MS m/z
294 (Mþ). Anal. Calcd for C17H14N2OS: C, 69.36; H, 4.79; N,
9.52. Found: C, 69.21; H, 4.92; N, 9.54.
(1H, m), 6.90 (1H, s), 7.19-7.30 (3H, m), 7.73-7.76 (1H, m); 13
C
NMR (100 MHz, CDCl3) δ 26.8 (q), 75.1 (d), 97.9 (d), 110.3 (d),
121.0 (d), 123.2 (s), 123.6 (d), 123.8 (d), 124.3 (t), 131.7 (s), 132.9
(s), 133.5 (s), 158.5 (s); MS m/z 213 (Mþ). Anal. Calcd for
C13H11DN2O: C, 73.22; H, 6.14; N, 13.14. Found: C, 73.34; H,
6.05; N, 13.01.
Synthesis of 4-Hydroxy-2,4-dimethyl-3,4-dihydropyrazino-
[1,2-a]indol-1(2H)-one (14). A mixture of allenamide 2 (1 mmol)
in toluene (10 mL) was heated at 150 °C for 1 h under microwave
irradiation, or refluxed for 24 h, then filtered on a Celite layer.
The solvent was evaporated under reduced pressure and the
crude residue was purified by flash chromatography. Yield
41%, white solid, mp 134 °C (i-Pr2O); IR 3313, 1652 cm-1; 1H
NMR (400 MHz, CDCl3) δ 1.78 (3H, s), 2.93 (3H, s), 3.49 (1H,
d, J = 12.6 Hz), 3.67 (1H, d, J = 12.6 Hz), 4.92 (1H, br s), 7.03
(1H, s), 7.10 (1H, dd, J = 8.5 Hz, 7.4 Hz), 7.22 (1H, dd, J = 7.9
Hz, 7.4 Hz), 7.52 (1H, d, J = 7.9 Hz), 7.83 (1H, d, J = 8.5 Hz);
13C NMR (100 MHz, CDCl3) δ 24.7 (q), 34.1 (q), 60.7 (t), 82.9
(s), 108.0 (d), 113.3 (d), 120.9 (d), 122.6 (d), 124.7 (d), 128.1 (s),
128.2 (s), 135.8 (s), 160.1 (s); MS m/z 230 (Mþ). Anal. Calcd for
C13H14N2O2: C, 67.81; H, 6.13; N, 12.17. Found: C, 67.66; H,
6.32; N, 11.97.
Acknowledgment. We acknowledge MIUR for financial
support (PRIN 2008KRBX3B) and the Ph.D. fellowship to
M.R. (Progetto Giovani 2006). We are also grateful to the
Centro Interuniversitario sulle Reazioni Pericicliche.
Supporting Information Available: 1H and 13C NMR spec-
tra for all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
6932 J. Org. Chem. Vol. 75, No. 20, 2010