Intramolecular Cyclization of Indole Derivatives
11.8 (br s, exch with D2O, 1H). 13C NMR (DMSO): δ 16.9, 36.4
(CH3), 113.3, 120.4, 123.0, 126.5, 127.6 (CHAr), 111.4, 123.2,
124.1, 128.1, 140.0, 155.4 (C). IR: 3150, 1651, 1589 cm-1. Anal.
Calcd for C13H12N2O: C, 73.57; H, 5.70; N, 13.20. Found: C,
73.55; H, 5.86; N, 13.07.
SCHEME 3
Da ta for 2b. Yield: 88%. Mp: 202-205 °C dec from CH2-
1
Cl2. H NMR: δ 2.65 (d, J ) 0.7 Hz, 3H), 4.86 (d, J ) 5.5 Hz,
2H), 5.25 (dd, J ) 1.5, 16.8 Hz, 1H), 5.33 (dd, J ) 1.5, 10.2
Hz, 1H), 6.04 (ddt, J ) 10.2, 16.8, 5.5 Hz, 1H), 6.89 (d, J ) 0.7
Hz, 1H), 7.27 (t, J ) 8.1 Hz, 1H), 7.51 (t, J ) 8.1 Hz, 1H), 7.68
(d, J ) 8.1 Hz, 1H), 8.12 (d, J ) 8.1 Hz, 1H), 10.95 (br s, exch
with D2O, 1H). 13C NMR: δ 16.9 (CH3), 50.6 (CH2), 113.2,
120.5, 122.5, 124.6, 126.5 (CHAr), 117.9 (CH2d), 133.4 (CH)),
113.9, 122.9, 125.1, 127.7, 140.3, 155.1 (C). IR: 3100, 1645,
1589 cm-1. Anal. Calcd for C15H14N2O: C, 75.61; H, 5.92; N,
11.76. Found: C, 75.51; H, 6.11; N, 11.75.
Da ta for 2c. Yield: 80%. Mp: >320 °C from CH2Cl2. 1H
NMR (DMSO): δ 2.55 (d, J ) 1.1 Hz, 3H), 7.14 (d, J ) 1.1 Hz,
1H), 7.22 (t, J ) 8.1 Hz, 1H), 7.40-7.52 (m, 6H), 7.57 (d, J )
8.1 Hz, 1H), 8.10 (d, J ) 8.1 Hz, 1H), 12.16 (br s, exch with
D2O, 1H). 13C NMR (DMSO): δ 17.0 (CH3), 112.3, 124.4, 127.6,
127.8, 140.3, 142.0, 155.1 (C), 113.6, 120.8, 123.2, 127.0, 127.3,
128.6 (CHAr), 128.1, 129.9 (2CHAr). IR: 3416, 1666, 1456
cm-1. Anal. Calcd for C18H14N2O: C, 78.81; H, 5.14; N, 10.21.
Found: C, 78.74; H, 5.23; N, 10.12.
the active catalyst species, but there is no experimental
evidence for this reaction. The base and the tetrabutyl-
ammonium chloride salt are essential to assist in the
regeneration of zerovalent palladium catalyst, and sev-
eral possible mechanisms could be envisaged.14 The salt
might act as a stabilizing agent by its chlorine anion
when there is no phosphine ligand in the reaction
mixture and as an accelerating agent by its onium cation.
In conclusion, in this paper we describe a catalytic
approach to aminations of nonactivated double bonds
which are still rare reactions. Furthermore, we have
demonstrated a high regioselectivity in a palladium-
catalyzed reaction of indole derivatives and focused on a
very efficient method to synthesize â-carbolinones 2 and
pyrazino[1,2-a]indole derivatives 3. Starting from olefin
derivatives of different nitrogen heterocycles, further
developments in this area are foreseen.
1
Da ta for 2d . Yield: 94%. Mp: 241-243 °C from Et2O. H
NMR: δ 1.45 (m, 2H), 1.67 (m, 4H), 2.01 (m, 4H), 2.66 (s, 3H),
5.19 (m, 1H), 6.96 (s, 1H), 7.26 (t, J ) 7.0 Hz, 1H), 7.50 (t, J
) 7.0 Hz, 1H), 7.65 (d, J ) 7.0 Hz, 1H), 8.11 (d, J ) 7.0 Hz,
1H), 10.56 (br s, exch with D2O, 1H). 13C NMR: δ 17.4 (CH3),
25.9 (CH2), 26.4, 33.2 (2CH2), 54.0 (CH), 113.2, 123.2, 124.1,
126.1, 140.2, 155.1 (C), 112.9, 120.1, 121.1, 122.7, 126.3
(CHAr). IR: 3106, 1651, 1582 cm-1
18H20N2O: C, 77.11; H, 7.19; N, 9.99. Found: C, 77.00; H,
7.26; N, 9.86.
. Anal. Calcd for
C
Syn th esis of 2,4-Disu bstitu ted 2H-P yr a zin o[1,2-a ]in -
d ol-1-on es 3a -d : Gen er a l P r oced u r e. To a solution of
4a -d (1 mmol) in DMF (5 mL) were added Pd(OAc)2 (12 mg,
5 mol %), tetrabutylammonium chloride (276 mg, 1 mmol), and
Na2CO3 (106 mg, 1 mmol). The mixture was heated at 100 °C
with stirring for the reported time. After completation of the
reaction the mixture was washed with brine and extracted
with Et2O (2 × 20 mL). The organic layer was dried with Na2-
SO4, filtered, and evaporated. The residue was purified by
silica gel column chromatography to give compounds 3a -d
(eluent see below).
Exp er im en ta l Section
Melting points were determined in open capillary tubes and
are uncorrected. IR spectra were recorded in Nujol mull for
solids and as a liquid film for oils. 1H NMR and 13C NMR
spectra were recorded in CDCl3 solution unless otherwise
stated. Chemical shifts are given in parts per million downfield
from SiMe4. Colum chromatography was performed on Kie-
selgel 60, 0.063-0.2 mm.
Rea ction of 3-Iod o-1H-in d ole-2-ca r boxylic Acid Allyl-
m eth yla m id e (1). To a solution of 1 (340 mg, 1 mmol) in DMF
(4 mL) were added AcOK (393 mg, 4 mmol), Pd(OAc)2 (11 mg,
5 mol %), and tetrapropylammonium bromide (266 mg, 1
mmol), Ph3P (39 mg, 15 mol %), and the mixture was heated
at 90 °C with stirring for 5 h. The mixture was then washed
with brine and extracted with Et2O (2 × 20 mL). The organic
layer was dried with Na2SO4, filtered, and evaporated. The
residue was purified by silica gel column chromatography,
eluent CH2Cl2/Et2O, 1:1, to afford 2a (62%) and 3a (17%).
Syn th esis of â-Ca r bolin on es 2a -d : Gen er a l P r oce-
d u r e. To a solution of 4a -d (1 mmol) in DMF (6 mL) and
THF (12 mL) were added PdCl2(CH3CN)2 (26 mg, 10 mol %)
and benzoquinone (108 mg, 1 mmol) under N2. The mixture
was stirred for 45 min at 80 °C and then concentrated in vacuo,
and the residue was poured into brine to give the â-carboli-
nones 2a -d . The filtrate was extracted with Et2O (2 × 20 mL)
and the solvent evaporated to give a residue which was
chromatographed on a silica gel column, eluent Et2O, to give
an additional amount of compounds 2a -d .
Da ta for 3a . Reaction time: 5.30 h. Eluent: CH2Cl2.
Yield: 74%. Mp: 183 °C from Et2O-hexane. 1H NMR: δ 2.77
(d, J ) 1.1 Hz, 3H), 3.50 (s, 3H), 6.08 (d, J ) 1.1 Hz, 1H),
7.30-7.40 (m, 2H), 7.51 (s, 1H), 7.85 (d, J ) 7.3 Hz, 1H), 8.02
(d, J ) 7.3 Hz, 1H). 13C NMR: δ 18.3, 34.6 (CH3), 104.1 (CHd
), 113.8, 114.1, 122.3, 122.9, 124.0 (CHAr), 118.5, 128.9, 129.3,
134.1, 157.0 (C). IR: 1640, 1463 cm-1. Anal. Calcd for
C
13H12N2O: C, 73.57; H, 5.70; N, 13.20. Found: C, 73.51; H,
5.68; N, 13.34.
Da ta for 3b. Reaction time: 2 h. Eluent: hexanes-Et2O,
1:1. Yield: 77%. Mp: 142-145 °C from Et2O-hexane. 1H
NMR: δ 2.77 (s, 3H), 4.54 (dd, J ) 1.1, 5.9 Hz, 2H), 5.26 (dd,
J ) 1.5, 14.7 Hz, 1H), 5.27 (dd, J ) 1.5, 11.3 Hz, 1H), 5.94 (m,
1H), 6.07 (s, 1H), 7.34 (m, 2H), 7.53 (s, 1H), 7.86 (d, J ) 8.1
Hz, 1H), 8.02 (d, J ) 8.1 Hz, 1H). 13C NMR: δ 18.5 (CH3),
48.7 (CH2), 104.7, 112.2, 114.1, 122.3, 123.0, 124.2 (CHAr),
132.9 (CHd), 118.5 (CH2d), 118.8, 128.9, 129.3, 134.1, 156.5
(C). IR:1651, 1582 cm-1. Anal. Calcd for C15H14N2O: C, 75.61;
H, 5.92; N, 11.76. Found: C, 75.02; H, 5.78; N, 11.84.
Da ta for 3c. Reaction time: 36 h. Eluent: hexanes-Et2O,
1:3. Yield: 65%. Mp: 150-153 °C from Et2O-hexane. 1H
NMR: δ 2.81 (s, 3H), 6.32 (s, 1H), 7.33-7.46 (m, 3H), 7.48-
7.56 (m, 4H), 7.61 (s, 1H), 7.87 (d, J ) 8.1 Hz, 1H), 8.06 (d, J
) 8.1 Hz, 1H). 13C NMR: δ 18.6 (CH3), 106.0, 114.0, 114.2,
122.5, 123.3, 124.6, 126.9, 127.2, 128.2, 129.5, 129.7 (CHAr),
99.5, 118.9, 129.1, 134.5, 140.3, 156.5 (C). IR: 1716, 1640, 1460
1
Da ta for 2a . Yield: 98%. Mp: 295 °C dec from CH2Cl2. H
NMR (acetone-d6): δ 2.60 (d, J ) 0.7 Hz, 3H), 3.66 (s, 3H),
7.08 (d, J ) 0.7 Hz, 1H), 7.24 (t, J ) 8.0 Hz, 1H), 7.46 (t, J )
8.0 Hz, 1H), 7.71 (d, J ) 8.0 Hz, 1H), 8.13 (d, J ) 8.0 Hz, 1H),
(14) J effery T. Tetrahedron 1996, 30, 10113-10130.
J . Org. Chem, Vol. 68, No. 20, 2003 7627