4
56
A. Arcadi et al.
LETTER
The latter can offer considerable potential for further elab-
oration by using palladium-catalyzed reactions. A couple
of examples are shown in Schemes 5 and 6.
Voorman, R. L.; Stefansky, K. J.; Stehle, R. G.; Tarpley, W.
G.; Morris, J. J. Med. Chem. 1998, 41, 1357.
3) (a) Rapoport, H.; Van Sickle, A. P. J. Org. Chem. 1990, 55,
(
(
895. (b) Hofmann, J. M. Jr. US Patent 45 4808595, 1989;
Chem Abst. 1989, 111, 115159m.
SiMe3
4) (a) Friedrichen, W. In Comprehensive Heterocyclic
Chemistry, Vol. 4; Katritzky, A. R.; Rees, C. W., Eds.;
Pergamon Press: New York, 1984, 974. (b) Shiotani, S.
Heterocycles 1997, 45, 975; and references therein.
Me
N
I
PdCl (PPh ) , CuI
Me
N
2
3 3
dioxane, Et3N, 45 °C
SiMe3
(79%)
O
OH
1b
9a
(c) Kitamura, T.; Tsuda, K.; Fujiwara, Y. Tetrahedron Lett.
NIS, KF,
68%) MeOH,
1998, 39, 5375.
(
(
(
5) Arcadi, A.; Cacchi, S.; Marinelli, F. Synthesis 1986, 749.
6) (a) Arcadi, A.; Cacchi, S.; Del Rosario, M.; Fabrizi, G.;
Marinelli, F. J. Org. Chem. 1996, 61, 9280. (b) Cacchi, S.;
Fabrizi, G.; Moro, L. Synlett 1998, 741. (c) Cacchi, S.;
Fabrizi, G.; Moro, L. Tetrahedron Lett. 1998, 39, 5101.
(d) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett
60 °C
Me
N
OH
Me
N
I
PdCl2(PPh3)2,
CuI, THF/Et3N,
O
O
1
999, 1432.
(7) (a) Typical procedure for the preparation of compounds
a,b: 3-Acetoxy-2-[2-(trimethylsilyl)ethynyl]pyridine 2a
r.t.
5j (83%)
10a
OH
3
7
b
(
2.36 g, 10.1 mmol) (prepared according to ref. ) was
dissolved in CH OH (20 mL) and KF (2.11 g, 36.4 mmol)
3
was added. The reaction mixture was stirred at room
temperature until TLC indicated complete consumption of
Scheme 5
2a. Then, the reaction mixture was concentrated under
vacuum and the residue was chromatographed on silica gel
eluting with an 80:20 (v/v) n-hexane–ethyl acetate mixture
to give 3a (0.83g, 70% yield); mp 144–145 °C; IR (KBr)
OH
SiMe
OH
3
)
3
PdCl
2
(PPh
3
3
, CuI
N, 45 °C
I
dioxane, Et
–1 1
3
280, 2100 cm ; H NMR 9.88 (bs, 1 H), 7.53 (dd, J = 5.8
SiMe3
1
3
N
(45%)
N
and 1.8 Hz, 1 H), 6.77 (m, 2 H), 3.83 (s, 1 H); C NMR
55.7, 140.7, 130.7, 124.7, 122.6, 83.7, 80.5; MS m/z
OH
O
1
Cl 1d
Cl
9b
+
(
relative intensity) 119 (M , 100), 91(53). Compound 3c was
NIS, KF,
51%) MeOH,
0 °C
prepared from 3-iodo-5-ethoxycarbonyl-2-pyridinol
according to ref. (b) Lindström, S.; Ripa, L.; Hallberg, A.
Org. Lett. 2000, 2, 2291.
(
1a
6
Pd(PPh
PhMe, K
0 °C
3
)
4
CO
OH
2
3
O
,
H
(8) A typical procedure for the preparation of 5 is as follows: To
a solution of 3a (0.047 g, 0.395 mmol), 4b (0.155 g, 0.592
8
mmol) in THF–Et N (2.0 mL/2.0 mL) under nitrogen,
Ph
I
3
N
N
PdCl (PPh ) (0.011 g, 0.016 mmol) and CuI (0.003 g, 0.016
PhB(OH)
2
2 3 2
O
O
mmol) were added. The mixture was stirred at room
temperature for 3 h. After cooling, the reaction mixture was
diluted with ethyl acetate and concentrated under vacuum.
The residue was chromatographed on silica gel eluting with
n-hexane–ethyl acetate (75:25 v/v) to afford 5b (0.084 g,
5k (86%)
Cl
Cl 10b
Scheme 6
8
4% yield); mp 181–182 °C; IR (KBr) 1730, 1610, 1560
–
1 1
cm ; H NMR 8.55 (m, 1H), 8.13 (d, J = 8.6 Hz, 2 H), 7.86
d, J = 8.6 Hz, 2 H), 7.32 (m, 1 H), 7.24 (s, 1 H), 7.21 (m, 1
Acknowledgement
(
This work was supported by the Ministero dell’Università e della
Ricerca Scientifica e Tecnologica (MURST - Roma) and Consiglio
Nazionale delle Ricerche (C.N.R.–Roma).
13
H), 3.94 (s, 3 H); C NMR 166.4, 158.1, 148.5, 148.2,
46.4, 133.5, 130.5, 130.1, 124.9, 119.4, 118.0, 104.3, 52.2;
1
+
MS m/z (relative intensity) 253 (M , 100), 222(81).
9) Niedballa, U. In Methoden der Organischen Chemie-
Houben-Weyl, Vol.V/2a; Müller, E., Ed.; Thieme: Stuttgart,
(
References
1
977, 925.
10) Böhm, V. P. W.; Herrmann, W. A. Eur. J. Org. Chem. 2000,
679.
11) Mori, A.; Shimada, T.; Kondo, T.; Sekiguchi, A. Synlett
001, 649.
(
(
(
1) (a) Houpis, I. N.; Choi, W. B.; Reider, P. J.; Molina, A.;
3
Churchill, H.; Lynch, J.; Volante, R. P. Tetrahedron Lett.
1994, 35, 9355. (b) Choi, W. B.; Houpis, I. N.; Churchill, H.
2
R. O.; Molina, A.; Lynch, J. E.; Volante, R. P.; Reider, P. G.;
King, A. O. Tetrahedron Lett. 1995, 36, 4571.
(
(
12) Aquila, B. M. Tetrahedron Lett. 1997, 38, 2795.
13) Typical procedure for the preparation of compounds 10: To
a solution of 1b (1.0 g, 4.25 mmol) and
(2) (a) Wishka, D. G.; Graber, D. R.; Seest, E. P.; Dolak, L. A.;
Han, F.; Watt, W.; Morris, J. J. Org. Chem. 1998, 63, 7851.
trimethylsilylacetylene (0.54 g, 5.53 mmol) in dioxane–Et N
(b) Wishka, D. G.; Graber, D. R.; Kopta, L. A.; Olmsted, R.
3
(
2.5 mL/2.5 mL) PdCl (PPh ) (0.045 g, 0.042 mmol) and
A.; Friis, J. M.; Hosley, J. D.; Adams, W. J.; Seest, E. P.;
Castle, T. M.; Dolak, L. A.; Keiser, B. A.; Yagi, Y.;
Jeganathan, A.; Schlachter, S. T.; Murphy, M. J.; Cleek, G.
J.; Nugent, R. A.; Poppe, S. M.; Swaney, S. M.; Han, F.;
Watt, W.; White, W. L.; Poel, T.-J.; Thomas, R. C.;
2 3 2
CuI (0.016 g, 0.084 mmol) were added under nitrogen. The
mixture was stirred at 45 °C for 3 h. After cooling, the
reaction mixture was diluted with ethyl acetate, washed with
HCl 0.1 M, dried over Na SO and concentrated under
2
4,
vacuum. The residue was chromatographed on silica gel
Synlett 2002, No. 3, 453–457 ISSN 0936-5214 © Thieme Stuttgart · New York