1
894
S. Cacchi et al.
PRACTICAL SYNTHETIC PROCEDURES
mmol), ttmpp (0.276 g, 0.52 mmol), and K CO (2.15 g, 15.57
this time, the mixture was cooled to r.t., poured into EtOAc (350
2
3
mmol) were added under argon. The reaction mixture was stirred at
0 °C for 3 h, until the disappearance of the starting alkyne (moni-
mL), washed with 0.1 HCl (10 mL) and H O (2 × 30 mL). The or-
2
8
ganic layer was dried (Na SO ) and concentrated under reduced
2
4
tored by TLC analysis). After this time, the mixture was cooled to
r.t., poured into EtOAc (350 mL), washed with 0.1 N HCl (10 mL)
and H O (2 × 30 mL). The organic layer was dried (Na SO ) and
concentrated under reduced pressure. The residue was purified by
flash chromatography (n-hexane–EtOAc, 85:15, Macherey-Nagel
silica gel 60, 0.025–0.040 mm, 100 g) to yield the indole product as
a pale yellow oil; yield: 1.049 g (72%).
pressure. The residue was purified by flash chromatography (n-hex-
ane–EtOAc, 50:50, Macherey-Nagel silica gel 60, 0.025–0.040
mm, 100 g) to yield the indole product as a brown powder; yield:
1.018 g (60%); mp 153–155 °C.
2
2
4
IR (KBr): 3200 (m), 1590 (s) cm–1.
1
H NMR (200 MHz, CDCl ): d = 8.70 (br s, 1 H), 7.86–7.80 (m, 1
3
H), 7.69 (d, J = 8.9 Hz, 2 H), 7.45–7.36 (m, 3 H), 7.31–7.16 (m, 5
–
1
IR (neat): 3384 (br), 3061 (m), 2983 (m), 1704 (s) cm .
H), 6.7 (d, J = 8.9 Hz, 2 H), 3.78 (s, 3 H).
1
H NMR (400 MHz, CDCl ): d = 8.25 (s, 1 H), 7.75–7.67 (m, 3 H),
13
3
C NMR (50.3 MHz, CDCl ): d = 192.5, 162.6, 143.0, 135.6,
3
7
.53–7.49 (m, 2 H), 7.47–7.35 (m, 2 H), 7.31–7.17 (m, 2 H), 4.21
1
1
32.2, 132.1, 131.7, 129.0, 128.6, 128.5, 128.3, 123.2, 121.7, 121.3,
13.6, 113.1, 111.3, 55.3.
(
q, J = 7.1 Hz, 2 H), 3.88 (s, 2 H), 1.30 (t, J = 7.1 Hz, 3 H).
1
3
C NMR (100.6 MHz, CDCl ): d = 172.3, 136.3, 135.9, 132.5,
+
3
MS (EI, 70 eV): m/z (%) = 327 (M , 88), 220 (100).
1
3
29.2, 129.0, 128.4, 128.1, 122.6, 120.1, 119.4, 111.0, 105.8, 50.9,
1.3, 14.3.
Anal. Calcd for C H NO : C, 80.71; H, 5.23; N, 4.28. Found: C,
22 17
2
8
0.54; H, 5.41; N, 4.52.
+
MS (EI, 70 eV): m/z (%) = 279 (M , 38), 206 (100),
Anal. Calcd for C H NO : C, 77.40; H, 6.13; N, 5.01. Found: C,
18
17
2
References
7
7.31; H, 6.11; N, 4.99.
(
(
(
(
1) For a recent review, see:Gribble, G. W. J. Chem. Soc.,
Perkin Trans. 1 2000, 1045.
2) Battistuzzi, G.; Cacchi, S.; Fabrizi, G. Eur. J. Org. Chem.
2
-Phenyl-3-cinnamylindole; Typical Procedure 3
A 100 mL round-bottom flask, equipped with a magnetic stirring
bar, was charged with 1a (1.5 g, 5.19 mmol) in anhyd THF (30 mL).
Cinnamyl carbonate (1.28 g, 6.22 mmol), Pd(PPh ) (0.299 g, 0.26
2
002, 2671.
3) Arcadi, A.; Cacchi, S.; Marinelli, F. Tetrahedron Lett. 1992,
3, 3915.
3
4
mmol), and K CO (3.58 g, 25.95 mmol) were added under argon.
2
3
3
The reaction mixture was stirred at 60 °C under argon for 3 h, until
the disappearance of the trifluoroacetanilide (monitored by TLC
analysis). Then, K CO (3.58 g, 25.95 mmol) was added and the
mixture was stirred at 80 °C for 24 h. The mixture was cooled to r.t.,
poured into EtOAc (350 mL) and washed with H O (3 × 25 mL).
The organic layer was dried (Na SO ) and concentrated under re-
4) (a) Sonogashira, K. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-WCH:
Weinheim, 1998, 203. (b) Sonogashira, K. In Handbook of
Organopalladium Chemistry for Organic Synthesis, Vol. 1;
Negishi, E., Ed.; Wiley: New York, 2002, 493.
2
3
2
2
4
(
5) o-Ethynyltrifluoroacetanilide can be prepared in 70%
overall yield from commercially available o-iodoaniline via
duced pressure. The residue was purified by flash chromatography
n-hexane–EtOAc, 95:5, Macherey-Nagel silica gel 60, 0.025–
(
0
1
3
a three-step process as described in Ref.
.040 mm, 100 g) to yield the indole product as a yellow oil; yield:
.49 g (93%).
(
6) Cacchi, S.; Fabrizi, G.; Lamba, D.; Marinelli, F.; Parisi, L.
M. Synthesis 2003, 728.
–
1
IR (neat): 3416 (br), 3056 (m), 3025 (m), 2924 (w), 1457 (s) cm .
(7) Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro, L.; Pace, P.
1
Synlett 1997, 1363.
H NMR (400 MHz, CDCl ): d = 8.12 (s, 1 H), 7.69 (d, J = 7.9 Hz,
3
(
8) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett
000, 394.
9) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett
000, 647.
(10) Cacchi, S.; Fabrizi, G.; Pace, P. J. Org. Chem. 1998, 63,
001.
2
H), 7.62 (dd, J = 7.1 Hz, J = 1.3 Hz, 2 H), 7.51 (t, J = 7.5 Hz, 2
1 2
2
H), 7.47–7.17 (m, 8 H), 6.58–6.51 (m, 2 H), 3.84 (d, J = 5.2 Hz, 2
H).
(
2
1
3
C NMR (100.6 MHz, CDCl ): d = 137.8, 136.1, 135.1, 133.0,
3
1
1
30.3, 129.8, 129.5, 129.0, 128.5, 128.0, 127.8, 127.0, 126.2, 122.5,
1
19.9, 119.6, 110.9, 110.7, 28.3.
(
11) (a) Arcadi, A.; Cacchi, S.; Carnicelli, V.; Marinelli, F.
Tetrahedron 1994, 50, 437. (b) See also: Cacchi, S.; Fabrizi,
G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (c) See also:
Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M.
Synlett 2001, 1605. (d) See also: Battistuzzi, G.; Cacchi, S.;
Fabrizi, G.; Marinelli, F.; Parisi, L. M. Org. Lett. 2002, 4,
+
MS (EI, 70 eV): m/z (%) = 309 (M , 100), 232 (16), 218 (62), 206
(
58), 193 (14).
Anal. Calcd for C H N: C, 89.28; H, 6.19; N, 4.53. Found: C,
8
2
3
19
9.19; H, 6.17; N, 4.54.
1
355.
2
-Phenyl-3-(4-methoxybenzoyl)indole; Typical Procedure 4
(
(
(
12) Saulnier, M. G.; Frennesson, D. B.; Deshpande, M. S.; Vyas,
D. M. Tetrahedron Lett. 1995, 36, 7841.
13) Flynn, B. L.; Hamel, E.; Jung, M. K. J. Med. Chem. 2002,
A 250 mL round-bottom flask, equipped with a magnetic stirring
bar, was charged with 1a (1.500 g, 5.19 mmol) in MeCN (60 mL).
4
mmol), and K CO (3.581 g, 25.95 mmol) were added under argon.
The flask was purged with CO for a few seconds, then connected to
a balloon of CO (Ø = 230 mm) and stirred at 45 °C overnight. After
-Iodoanisole (1.821 g, 7.78 mmol), Pd(PPh3)4 (0.299 g, 0.26
4
5, 2670.
14) Colllini, M. D.; Ellingboe, J. W. Tetrahedron Lett. 1997, 38,
963.
2
3
7
Synthesis 2004, No. 11, 1889–1894 © Thieme Stuttgart · New York