Pd-catalyzed intramolecular cyclization of pyrrolo-2-carboxamides: Regiodivergent routes to pyrrolo-pyrazines and pyrrolo-pyridines

Article abstract of DOI:10.1016/j.tet.2004.11.066

Treatment of N-alkyl-N-allyl-pyrrolo-2-carboxamides with catalytic amounts of palladium derivatives gave regioselectively intramolecular cyclizations to generate bicyclic pyrrolo-fused structures. Pyrrolo[1,2-a]pyrazin-1-ones were achieved in high yields

Full text of DOI:10.1016/j.tet.2004.11.066

Tetrahedron 61 (2005) 1077–1082
Pd-catalyzed intramolecular cyclization of
pyrrolo-2-carboxamides: regiodivergent routes to
pyrrolo-pyrazines and pyrrolo-pyridines
b
a
Egle M. Beccalli,a Gianluigi Broggini,b, Michela Martinelli and Giuseppe Paladino
*
a
` `
Istituto di Chimica Organica ‘A. Marchesini’, Facolta di Farmacia, Universita di Milano, via Venezian 21, 20133 Milano, Italy
b
`
Dipartimento di Scienze Chimiche e Ambientali, Universita dell’Insubria, via Valleggio 11, 22100 Como, Italy
Received 24 September 2004; revised 4 November 2004; accepted 25 November 2004
Available online 10 December 2004
Abstract—Treatment of N-alkyl-N-allyl-pyrrolo-2-carboxamides with catalytic amounts of palladium derivatives gave regioselectively
intramolecular cyclizations to generate bicyclic pyrrolo-fused structures. Pyrrolo[1,2-a]pyrazin-1-ones were achieved in high yields by an
amination reaction, while pyrrolo[2,3-c]pyridin-7-ones and pyrrolo[3,2-c]pyridin-4-ones were obtained by an oxidative coupling process.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
process in the light of the possibility of reaction at the 1- and
3-positions of the pyrrole nucleus.
Nitrogen-containing heterocycles have always constituted a
subject of great interest due to their wide presence in
biologically important compounds. Also in this field, the
catalysis by palladium has become a powerful arm in the
hands of the organic chemists.1 All typologies of Pd-
catalysis have been successfully employed: Heck2 and
Buchwald–Hartwig3 protocols, cross coupling reactions,4
alkene and alkyne amination,5 oxidative coupling.6
2. Results and discussion
As a model substrate, the unknown N-allyl-N-methyl-2-
carboxamide 2a was easily prepared starting from the
pyrrole-2-carboxylic acid (Scheme 1). The first cyclization
path, involving the pyrrolic nitrogen so giving the
pyrrolo[1,2-a]pyrazine skeleton, was attained in 62% with
10 mol% of Pd(OAc)2 as catalyst and DMSO as solvent at
100 8C, in presence of AcONa and tetrabutylammonium
chloride. This latter, as well as a polar aprotic solvent, was
essential to attain a satisfactory yield.
As a part of an ongoing program directed to the
development of palladium-catalyzed intramolecular cycli-
zations, we already reported efficient methods for the
construction of b- and g-carbolinones,7–9 pyrazino[1,2-
a]indoles,9 quinazolinones and 1,4-benzodiazepin-5-ones,10
dibenzodiazepinones and pyridobenzodiazepinones.11
This amination process involves Pd(0) species as
confirmed by its inhibition when operating in presence of
p-benzoquinone as reoxidant agent. In this case, only
unreacted starting material was recovered. However, the use
of p-benzoquinone in different reaction conditions led to a
new outcome involving the C-3 position of the pyrrolic
ring to give a pyrrolo-pyridine skeleton by way of an
oxidative coupling. More precisely, operating with PdCl2-
(CH3CN)2 (10 mol%) as catalyst and a stoichiometric
amount of p-benzoquinone in a mixture DMF/THF as
solvent, the compound 2a was totally converted in a 1:1
mixture of two products, isolated in 30 and 35% yields,
respectively. The isomeric structures 4a and 5a were
assigned on the base of the analytical and spectroscopic
data. The diagnostic evidence to distinguish between the
In the wide range of Pd-catalyzed reactions known today,
aryl- and vinyl-halides have been employed more than
unhalogenated substrates despite them suffering from a
general difficulty of synthesis. In an effort to expand the
access to new nitrogenated heteropolycycles, we studied the
behavior of N-alkyl-N-allyl-pyrrolo-2-carboxamides
towards Pd-catalyzed intramolecular cyclizations. Particu-
lar interest came from the regioselective aspect of the
Keywords: Amination; Fused-pyrrole system; Cyclization reactions;
Palladium; Regioselectivity.
* Corresponding author. Tel.: C39 031 2386441; fax: C39 031 2386449;
e-mail: gianluigi.broggini@uninsubria.it
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.11.066

1078
E. M. Beccalli et al. / Tetrahedron 61 (2005) 1077–1082
pyrrolo[2,3-c]pyridin-7-one (4a) and the pyrrolo[3,2-c]-
pyridine-4-one (5a) resulted from the 1H NMR and IR
spectra. The chemical shift of the NH proton resonates at
10.21 d in the former suffering of the deshielding effect of
the carbonyl group, in comparison with the NH signal at
9.08 d in the latter. On the other hand, the infrared frequency
of the carbonyl group stretch is greater in compound 4a with
respect to 5a according to analogue structures reported in
the literature.12
A plausible mechanism, although highly speculative, is
shown in Scheme 2. The olefin–palladium complex A would
undergo the nucleophilic attack by the 2-carbon of the
electron-rich pyrrole nucleus to give the transient spiro-
derivative B. The latter would rearomatize through an
anionotropic shift and subsequent loss of a proton.
However, both s bonds at the spiranic center are able to
migrate so that two different skeleton types are formed,
namely the Pd-s-complexes C (path (i)) and D (path (ii)).
The subsequent b-elimination afforded unisolable exo-
methylenic compounds by loss of hydrochloride acid and
Pd(0). Double bond migration inside the six-membered ring
originated the thermodynamically more stable structures 4a
or 5a. Finally, it must be underlined as the palladium can go
back to the catalytic cycle after reoxidation due to the
presence of the p-benzoquinone. The alternative pathway
assuming a Heck type mechanism with aromatic pallada-
tion,6j though consistent with compound 4a, does not justify
the isomeric compound 5a. In any case, we do not rule out
both the mechanisms may be operating.
Scheme 1.
Given these results, both the reactions of amination and
oxidative coupling were carried out with various substrates
accessible from commercial alkyl–allyl-amines 1b–e. The
Scheme 2.

E. M. Beccalli et al. / Tetrahedron 61 (2005) 1077–1082
Table 1. Yields (%) of the intramolecular cyclization products 3–5a–e
1079
Entry
R
3a
4b
5b
a
b
c
d
e
Methyl
Allyl
Phenyl
Cyclohexyl
Cyclopentyl
62
85
57
89
82
30
33
27
38
29
35
31
41
45
48
a Reaction conditions: Pd(OAc)2, AcONa, Bu4NCl, DMSO.
b Reaction conditions: PdCl2(CH3CN)2, p-benzoquinone, DMF/THF.
latter gave the amides 2b–e in 67–93% yields, the behavior
of which resulted analogue to the model 2a. The cyclization
yields (collected in Table 1) were not significantly affected
by the N-substituents.
calcd for C9H12N2O: C, 65.83; H, 7.37; N, 17.06. Found C,
65.92; H, 7.25; N, 16.87.
3.2.2. N,N-Diallyl-pyrrolo-2-carboxamide (2b). Eluent:
AcOEt/light petroleum 1:4. Yield: 69%. Mp 63–64 8C (from
In summary, using catalytic amount of palladium, we have
developed regioselective cyclization conditions of N-allyl-
pyrrolo-2-carboxamides to access to different pyrrolo-fused
heterocycles. Pyrrolo[1,2-a]pyrazin-1-ones were generated
in very high yields by an amination process when the Pd(0)
species is at work. Conversely, pyrrolo[2,3-c]pyridin-7-ones
and pyrrolo[3,2-c]pyridin-4-ones were formed by an
oxidative coupling when using Pd(II) in the presence of
an oxidant.
diisopropyl ether). IR (nujol): 1649 cmK1 1H NMR
;
(400 MHz, CDCl3): dZ4.19 (4H, br.s), 5.16–5.24 (4H,
overlapping), 5.86–5.95 (2H, overlapping), 6.24 (1H, dd,
JZ2.3, 2.6 Hz), 6.60 (1H, d, JZ2.3 Hz), 6.93 (1H, d, JZ
2.6 Hz), 9.80 (1H, br.s). 13C NMR (100 MHz, CDCl3): dZ
50.0 (t), 109.6 (d), 112.9 (d), 117.5 (t), 122.5 (d), 124.6 (s),
133.7 (d), 163.6 (s). Anal. calcd for C11H14N2O: C, 69.45;
H, 7.42; N, 14.72. Found C, 69.56; H, 7.25; N, 14.80.
3.2.3. N-Allyl-N-phenyl-pyrrolo-2-carboxamide (2c).
Eluent: AcOEt/light petroleum 4:1. Yield: 81%. Mp 117–
118 8C (from diisopropyl ether). IR (nujol): 1653 cmK1; 1H
NMR (400 MHz, CDCl3): dZ4.45 (2H, d, JZ6.2 Hz), 4.90
(1H, br.s), 5.15 (1H, d, JZ16.9 Hz), 5.18 (1H, d, JZ
10.3 Hz), 5.90–6.12 (2H, overlapping), 6.83 (1H, br.s),
7.25–7.31 (2H, overlapping), 7.43–7.53 (3H, overlapping),
9.75 (1H, br.s). 13C NMR (100 MHz, CDCl3): dZ53.8 (t),
110.0 (d), 114.3 (d), 118.3 (t), 121.5 (d), 125.4 (s), 128.7 (d),
129.5 (d), 130.0 (d), 133.6 (d), 143.2 (s), 161.5 (s). Anal.
calcd for C14H14N2O: C, 74.31; H, 6.24; N, 12.38. Found C,
74.22; H, 6.43; N, 12.29.
3. Experimental
3.1. General
Preparative column chromatography was carried out on
silica gel 60 (Merck) (mesh size 63–200 mm). Melting
points were measured on a Bu¨chi B-540 heating unit and are
not corrected. NMR spectra were recorded on an AVANCE
400 Bruker. IR spectra were taken on a Jasco FT/IR 5300
spectrophotometer.
3.2.4. N-Allyl-N-cyclohexyl-pyrrolo-2-carboxamide (2d).
Eluent: AcOEt/light petroleum 1:5. Yield: 68%. Mp 109–
110 8C (from diisopropyl ether). IR (nujol): 1645 cmK1; 1H
NMR (400 MHz, CDCl3): dZ1.09–1.20 (1H, m), 1.27–1.48
(2H, overlapping), 1.50–1.62 (2H, overlapping), 1.65–1.75
(1H, m), 1.78–1.85 (4H, overlapping), 4.18 (2H, d, JZ
5.2 Hz), 4.43 (1H, tt, JZ3.1, 11.9 Hz), 5.19 (1H, d, JZ
10.0 Hz) 5.26 (1H, d, JZ17.4 Hz), 5.92 (1H, tdd, JZ5.2,
10.0, 17.4 Hz), 6.24 (1H, d, JZ2.9 Hz), 6.56 (1H, br.s), 6.93
(1H br.s), 10.34 (1H, br.s). 13C NMR (100 MHz, CDCl3):
dZ26.0 (t), 26.4 (t), 31.5 (t), 46.7 (d), 56.8 (t), 109.6 (d),
112.3 (d), 116.3 (t), 121.7 (d), 125.5 (s), 136.6 (d), 163.1 (s).
Anal. calcd for C14H20N2O: C, 72.38; H, 8.68; N, 12.06.
Found C, 74.41; H, 8.52; N, 12.12.
3.2. General procedure for the preparation of
allylamides 2a–e
A solution of 2-pyrrole-carboxylic acid (1.07 g, 9.6 mmol)
and SOCl2 (3.49 ml, 48 mmol) in toluene (30 ml) was
refluxed for 4 h. After evaporation of the solvent, the crude
mixture was taken up with CH2Cl2 (10 ml), then a solution
of 1a–e (14.4 mmol) and TEA (1.35 ml, 9.6 mmol) in
CH2Cl2 (6 ml) was dropped at 0 8C. The resultant solution
was stirred at room temperature for 2 h, then washed with
5% HCl (2!25 ml) and 5% aqueous NaOH (2!25 ml).
The organic layer was dried over Na2SO4 and the solvent
evaporated under reduced pressure. The crude product was
chromatographed on a silica gel column to give compounds
2a–e.
3.2.5. N-Allyl-N-cyclopenthyl-pyrrolo-2-carboxamide
(2e). Eluent: AcOEt/light petroleum 1:6. Yield: 67%. Mp
3.2.1. N-Allyl-N-methyl-pyrrolo-2-carboxamide (2a).
Eluent: Et2O/light petroleum 1:4. Yield: 93%. Mp 55–
94–95 8C (from diisopropyl ether). IR (nujol): 1650 cmK1
;
1H NMR (400 MHz, CDCl3): dZ1.53–1.82 (6H, overlap-
ping), 1.85–2.09 (2H, overlapping), 4.16 (2H, d, JZ4.5 Hz),
4.78–4.89 (1H, m), 5.23 (1H, d, JZ12.3 Hz), 5.27 (1H, d,
JZ18.4 Hz), 5.94 (1H, tdd, JZ4.5, 12.3, 18.4 Hz), 6.22
(1H, ddd, JZ2.6, 2.7, 2.9 Hz), 6.60 (1H, br.s), 6.92 (1H,
br.s), 10.50 (1H, br.s). 13C NMR (100 MHz, CDCl3): dZ
24.2 (t), 24.3 (t), 47.2 (d), 58.8 (t), 109.6 (d), 112.3 (d),
116.3 (t), 121.7 (d), 125.5 (s), 136.1 (d), 163.6 (s). Anal.
56 8C (from diisopropyl ether). IR (nujol): 1647 cmK1; H
1
NMR (400 MHz, CDCl3): dZ3.20 (3H, s), 4.23 (2H, d, JZ
4.4 Hz), 5.24 (1H, d, JZ10.5 Hz), 5.26 (1H, d, JZ17.1 Hz),
5.91 (1H, tdd, JZ4.4, 10.5, 17.1 Hz), 6.24–6.29 (1H, m),
6.61 (1H, br.s), 6.95 (1H, br.s), 9.57 (1H, br.s). 13C NMR
(100 MHz, CDCl3): dZ34.6 (q), 46.2 (t), 109.9 (d), 113.0
(d), 117.5 (t), 121.8 (d), 125.1 (s), 133.4 (d), 160.3 (s). Anal.

1080
E. M. Beccalli et al. / Tetrahedron 61 (2005) 1077–1082
calcd for C13H18N2O: C, 71.53; H, 8.31; N, 12.83. Found C,
71.39; H, 8.51; N, 12.92.
82%. Oil. IR (nujol): 1638 cmK1 1H NMR (400 MHz,
;
CDCl3): dZ1.55–1.94 (6H, overlapping), 2.03–2.19 (2H,
overlapping), 2.34 (3H, s), 5.37 (1H, dddd, JZ8.2, 8.2, 8.2,
8.2 Hz), 6.21 (1H, s), 6.61 (1H, dd, JZ3.2, 3.8 Hz), 7.07
(1H, br.s), 7.16 (1H, d, JZ3.9 Hz). 13C NMR (100 MHz,
CDCl3): dZ15.5 (q), 25.0 (t), 31.8 (t), 54.0 (d), 110.7 (d),
111.0 (d), 112.9 (d), 115.7 (d), 116.3 (s), 124.7 (s), 156.2 (s).
Anal. calcd for C13H16N2O: C, 72.19; H, 7.46; N, 12.95.
Found C, 72.11; H, 7.53; N, 12.83.
3.3. General procedure for the cyclization to give
pyrrolo[1,2-a]pyrazin-1-ones 3a–e
To a solution of 2a–e (1 mmol) in DMSO (5 ml), AcONa
(82 mg, 1 mmol), Bu4NCl (277 mg, 1 mmol) and Pd(OAc)2
(22.4 mg, 0.1 mmol) were added. The mixture was stirred
for 72 h at 120 8C. The solution was washed with brine
(50 ml) and extracted with Et2O (2!50 ml). The organic
layer was dried over Na2SO4 and taken to dryness under
reduced pressure. The residue was chromatographed on a
silica gel column to give 3a–e.
3.4. General procedure for the cyclization to give
pyrrolo[2,3-c]pyridin-7-ones (4a–e) and pyrrolo[3,2-c]-
pyridin-4-ones (5a–e)
To a solution of 2a–e (1 mmol) in DMF (6 ml) and THF
(12 ml), PdCl2(CH3CN)2 (389 mg, 0.15 mmol) and
p-benzoquinone (108, 1 mmol) were added under N2. The
mixture was stirred for 18 h at 100 8C, then poured into
brine (30 ml) and extracted with Et2O (2!25 ml). The
solvent evaporated to give a residue that was chromato-
graphed on silica gel column to give the compounds 4a–e
and 5a–e.
3.3.1. 2,4-Dimethyl-2H-pyrrolo[1,2-a]pyrazin-1-one
(3a). Eluent: Et2O/light petroleum 1:4. Yield: 62%. Oil.
1
IR (nujol): 1653 cmK1; H NMR (400 MHz, CDCl3): dZ
2.31 (3H, s), 3.46 (3H, s), 6.20 (1H, s), 6.62 (1H, dd, JZ2.7,
3.9 Hz), 7.08 (1H, dd, JZ1.6, 2.7 Hz), 7.18 (1H, dd, JZ1.6,
3.9 Hz). 13C NMR (100 MHz, CHCl3): dZ14.9 (q), 41.2
(q), 110.6 (d), 112.8 (d), 115.8 (s), 115.9 (d), 116.1 (d),
124.7 (s), 156.4 (s). Anal. calcd for C9H10N2O: C, 66.65; H,
6.21; N, 17.27. Found C, 66.60; H, 6.45; N, 17.32.
Entry a. Elution with CH2Cl2/MeOH 10:1 gave 4a (30%)
and 5a (35%).
3.3.2. 2-Allyl-4-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one
(3b). Eluent: Et2O/light petroleum 1:4. Yield: 85%. Oil.
3.4.1. 4,6-Dimethyl-1,6-dihydro-pyrrolo[2,3-c]pyridin-7-
ones (4a). Mp 238–239 8C (from diisopropyl ether). IR
1
IR (nujol): 1655 cmK1; H NMR (400 MHz, CDCl3): dZ
1
(nujol): 3394, 1655 cmK1; H NMR (400 MHz, CDCl3):
2.30 (3H, s), 4.49 (2H, d, JZ5.8 Hz), 5.21 (1H, d, JZ
16.5 Hz), 5.25 (1H, d, JZ11.3 Hz), 5.93 (1H, tdd, JZ5.8,
11.3, 16.5 Hz), 6.17 (1H, s), 6.61 (1H, dd, JZ2.4, 2.9 Hz),
7.08 (1H, dd, JZ1.8, 2.4 Hz) 7.18 (1H, dd, JZ1.8, 2.9 Hz).
13C NMR (100 MHz, CDCl3): dZ15.1 (q), 48.9 (t), 111.7
(d), 112.9 (d), 114.4 (d), 116.3 (d), 116.1 (s), 118.4 (t), 124.6
(s), 133.4 (d), 155.9 (s). Anal. calcd for C11H12N2O: C,
70.19; H, 6.43; N, 14.88. Found C, 70.29; H, 6.25; N, 14.97.
dZ2.26 (3H, s), 3.67 (3H, s), 6.41 (1H, dd, JZ2.3, 2.5 Hz),
6.74 (1H, s), 7.31 (1H, d, JZ2.3 Hz), 10.21 (1H, br.s). 13C
NMR (100 MHz, CDCl3): dZ15.6 (q), 36.4 (q), 102.0 (d),
112.0 (s), 123.8 (s), 126.3 (d), 127.5 (d), 132.5 (s), 155.6 (s).
Anal. calcd for C9H10N2O: C, 66.65; H, 6.21; N, 17.27.
Found C, 66.49; H, 6.35; N, 17.13.
3.4.2. 5,7-Dimethyl-1,5-dihydro-pyrrolo[3,2-c]pyridin-4-
ones (5a). Mp 243–245 8C (from diisopropyl ether). IR
3.3.3. 4-Methyl-2-phenyl-2H-pyrrolo[1,2-a]pyrazin-1-
one (3c). Eluent: AcOEt/light petroleum 1:4. Yield: 57%.
1
(nujol): 3260, 1651 cmK1; H NMR (400 MHz, CDCl3):
1
Oil. IR (nujol): 1645 cmK1; H NMR (400 MHz, CDCl3):
dZ2.27 (3H, s), 3.62 (3H, s), 6.85 (1H, s), 6.88 (1H, dd, JZ
2.5, 2.6 Hz), 7.03 (1H, dd, JZ2.6, 2.6 Hz), 9.08 (1H, br.s).
13C NMR (100 MHz, CDCl3): dZ13.7 (q), 36.9 (q), 105.3
(s), 106.1 (d), 115.3 (s), 122.2 (d), 129.7 (d), 139.7 (s), 160.0
(s). Anal. calcd for C9H10N2O: C, 66.65; H, 6.21; N, 17.27.
Found C, 66.47; H, 6.38; N, 17.12.
dZ2.36 (3H, s), 6.42 (1H, s), 6.68 (1H, dd, JZ3.6, 2.8 Hz),
7.16 (1H, d, JZ2.8 Hz), 7.28 (1H, d, JZ3.6 Hz), 7.33–7.55
(5H, overlapping). 13C NMR (100 MHz, CDCl3): dZ15.1
(q), 112.4 (d), 113.2 (d), 116.0 (d), 116.1 (s), 116.7 (d),
124.7 (s), 127.1 (d), 128.1 (d), 129.7 (d), 140.6 (s), 155.6 (s).
Anal. calcd for C14H12N2O: C, 74.98; H, 5.39; N, 12.49.
Found C, 74.87; H, 5.59; N, 12.57.
Entry b. Elution with CH2Cl2/MeOH 10:1 gave 4b (33%)
and 5b (31%).
3.3.4. 2-Cyclohexyl-4-methyl-2H-pyrrolo[1,2-a]pyrazin-
1-one (3d). Eluent: AcOEt/light petroleum 1:4. Yield: 89%.
3.4.3. 6-Allyl-4-methyl-1,6-dihydro-pyrrolo[2,3-c]pyri-
din-7-ones (4b). Mp 211–212 8C (from diisopropyl ether).
IR (nujol): 3389, 1657 cmK1; 1H NMR (400 MHz, CDCl3):
dZ2.27 (3H, s), 4.72 (2H, d, JZ5.6 Hz), 5.17 (1H, d, JZ
17.1 Hz), 5.24 (1H, d, JZ10.2 Hz), 6.02 (1H, ddd, JZ5.6,
10.2, 17.1 Hz), 6.37 (1H, br.s), 6.70 (1H, s), 7.30 (1H, br.s),
10.48 (1H, br.s). 13C NMR (100 MHz, CHCl3): dZ15.7 (q),
50.3 (t), 102.1 (d), 112.3 (s), 117.6 (t), 123.8 (s), 125.1 (d),
127.5 (d), 132.5 (s), 134.1 (d), 155.0 (s). Anal. calcd for
C11H12N2O: C, 70.19; H, 6.43; N, 14.88. Found C, 70.24; H,
6.33; N, 15.00.
1
Oil. IR (nujol): 1624 cmK1; H NMR (400 MHz, CDCl3):
dZ1.10–1.35 (1H, m), 1.42–1.65 (4H, overlapping), 1.67–
1.79 (1H, m), 1.83–1.95 (4H, overlapping), 2.32 (3H, s),
4.76–4.85 (1H, m), 6.26 (1H, s), 6.61 (1H, dd, JZ2.8,
3.7 Hz), 7.07 (1H, dd, JZ1.1, 2.8 Hz), 7.17 (1H, dd, JZ1.1,
3.7 Hz). 13C NMR (100 MHz, CDCl3): dZ15.4 (q), 25.7 (t),
26.1 (t), 32.4 (t), 52.1 (d), 110.7 (d), 110.9 (d), 112.8 (d),
115.6 (d), 115.7 (s) 124.8 (s) 155.7 (s). Anal. calcd for
C14H18N2O: C, 73.01; H, 7.88; N, 12.16. Found C, 72.93; H,
8.02; N, 12.12.
3.3.5. 2-Cyclopenthyl-4-methyl-2H-pyrrolo[1,2-a]pyra-
zin-1-one (3e). Eluent: AcOEt/light petroleum 1:7. Yield:
3.4.4. 5-Allyl-7-methyl-1,5-dihydro-pyrrolo[3,2-c]pyri-
din-4-ones (5b). Mp 86–87 8C (from diisopropyl ether).

E. M. Beccalli et al. / Tetrahedron 61 (2005) 1077–1082
1081
1
IR (nujol): 3270, 1649 cm–1; H NMR (400 MHz, CDCl3):
C14H18N2O: C, 73.01; H, 7.88; N, 12.16. Found C, 72.98; H,
7.95; N, 12.13.
dZ2.26 (3H, s), 4.67 (2H, d, JZ5.6 Hz), 5.16 (1H, d, JZ
17.1 Hz), 5.21 (1H, d, JZ10.3 Hz), 5.99 (1H, ddd, JZ5.6,
10.3, 17.1 Hz), 6.81 (1H, s), 6.88 (1H, dd, JZ2.6, 2.6 Hz),
7.01 (1H, dd, JZ2.6, 2.7 Hz), 8.80 (1H, br.s); 13C NMR
(100 MHz, CDCl3): dZ13.7 (q), 50.4 (t), 105.1 (s), 106.5
(d), 115.7 (s), 117.7 (t), 121.9 (d), 128.5 (d), 134.3 (d), 139.4
(s), 159.7 (s). MS: m/z 188 (MC). Anal. calcd for
C11H12N2O: C, 70.19; H, 6.43; N, 14.88. Found C, 70.16;
H, 6.55; N, 14.73.
Entry e. Elution with CH2Cl2/MeOH 27:1 gave 4e (29%)
and 5e (48%).
3.4.9. 6-Cyclopentyl-4-methyl-1,6-dihydro-pyrrolo[2,3-
c]pyridin-7-ones (4e). Mp 119–120 8C (from diisopropyl
1
ether). IR (nujol): 3385, 1653 cmK1; H NMR (400 MHz,
CDCl3): dZ1.66–1.82 (4H, overlapping), 1.83–2.00 (2H,
overlapping), 2.14–2.28 (2H, overlapping), 2.29 (3H, s),
5.53 (1H, dddd, JZ8.1 Hz), 6.37 (1H, br.s), 6.77 (1H, s),
7.27 (1H, br.s), 10.66 (1H, br.s). 13C NMR (100 MHz,
CDCl3): dZ16.0 (q), 25.1 (t), 32.8 (t), 55.2 (d), 102.2 (d),
112.2 (s), 121.4 (d), 123.7 (s), 127.0 (d), 131.5 (s), 155.2 (s).
Anal. calcd for C13H16N2O: C, 72.19; H, 7.46; N, 12.95.
Found C, 72.02; H, 7.53; N, 12.99.
Entry c. Elution with CH2Cl2/MeOH 15:1 gave 4c (27%)
and 5c (41%).
3.4.5. 4-Methyl-6-phenyl-1,6-dihydro-pyrrolo[2,3-c]-
pyridin-7-ones (4c). Mp 128–129 8C (from diisopropyl
ether). IR (nujol): 3385, 1660 cmK1; H NMR (400 MHz,
1
CDCl3): dZ2.30 (3H, s), 6.43 (1H, br.s), 6.84 (1H, s), 7.28
(1H, br.s), 7.35–7.55 (5H, overlapping), 10.75 (1H, br.s).
13C NMR (100 MHz, CDCl3): dZ15.5 (q), 102.7 (d), 107.9
(s), 123.6 (s), 126.6 (d), 127.6 (d), 127.7 (d), 128.3 (d),
129.5 (d), 132.7 (s), 141.7 (s), 155.1 (s). Anal. calcd for
C14H12N2O: C, 74.98; H, 5.39; N, 12.49. Found C, 74.89; H,
5.43; N, 12.52.
3.4.10. 5-Cyclopentyl-7-methyl-1,5-dihydro-pyrrolo[3,2-
c]pyridin-4-ones (5e). Mp 135–136 8C (from diisopropyl
1
ether). IR (nujol): 3256, 1641 cmK1; H NMR (400 MHz,
CDCl3): dZ1.52–1.83 (4H, overlapping), 1.84–2.01 (2H,
overlapping), 2.10–2.28 (2H, overlapping), 2.29 (3H, s),
5.53 (1H, dddd, JZ8.0 Hz), 6.88 (1H, dd, JZ2.3, 2.6 Hz),
6.90 (1H, s), 7.01 (1H, dd, JZ2.6, 2.7 Hz), 9.22 (1H, br.s).
13C NMR (100 MHz, CDCl3): dZ14.2 (q), 25.0 (t), 32.9 (t),
55.4 (d), 106.5 (d), 115.1 (s), 116.6 (d), 124.9 (d), 139.1 (s),
150.1 (s), 159.9 (s). Anal. calcd for C13H16N2O: C, 72.19;
H, 7.46; N, 12.95. Found C, 72.05; H, 7.56; N, 12.97.
3.4.6. 7-Methyl-5-phenyl-1,5-dihydro-pyrrolo[3,2-c]-
pyridin-4-ones (5c). Mp 83–84 8C (from diisopropyl
1
ether). IR (nujol): 3268, 1651 cmK1; H NMR (400 MHz,
CDCl3): dZ2.23 (3H, s), 6.87 (1H, dd, JZ2.6, 2.6 Hz), 6.90
(1H, br.s), 6.97 (1H, dd, JZ2.6, 2.8 Hz), 7.32–7.54 (5H,
overlapping), 9.27 (1H, br.s). 13C NMR (100 MHz, CDCl3):
dZ13.7 (q), 106.1 (d), 106.3 (s), 115.3 (s), 123.0 (d), 127.8
(d), 128.2 (d), 129.3 (d), 129.4 (d), 140.0 (s), 142.2 (s),
160.1 (s). Anal. calcd for C14H12N2O: C, 74.98; H, 5.39; N,
12.49. Found C, 75.03; H, 5.25; N, 12.52.
Acknowledgements
We are grateful to MURST for financial support.
Entry d. Elution with CH2Cl2/MeOH 20:1 gave 4d (38%)
and 5d (45%).
References and notes
3.4.7. 6-Cyclohexyl-4-methyl-1,6-dihydro-pyrrolo[2,3-
c]pyridin-7-ones (4d). Mp 120–121 8C (from diisopropyl
1. (a) Li, J. J.; Gribble, G. W. Palladium in Heterocyclic
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1
ether). IR (nujol): 3396, 1655 cmK1; H NMR (400 MHz,
CDCl3): dZ1.15–1.40 (1H, m), 1.42–1.67 (4H, over-
lapping), 1.74–1.83 (1H, m), 1.91–2.01 (4H, overlapping),
2.30 (3H, s), 5.03 (1H, tt, JZ3.2, 11.6 Hz), 6.39 (1H, dd JZ
2.4, 2.7 Hz,), 6.82 (1H, s), 7.29 (1H, dd JZ2.7, 2.7 Hz),
10.35 (1H, br.s). 13C NMR (100 MHz, CDCl3): dZ16.0 (q),
25.9 (t), 30.1 (t), 33.3 (t), 53.9 (d), 102.3 (d), 112.3 (s), 121.4
(d), 127.4 (s), 127.6 (d), 130.7 (s), 150.5 (s). Anal. calcd for
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7.72; N, 12.25.
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