Table 1
Entry
X
A
Catalyst
Solvent/base
T/ЊC
Yield (%)
1
2
3
4
2a SnBu3
2b l
3b Br
3c ZnCl
3a H
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4–PPh3–Cul
PPh3–Cul
DMF
THF
CH3CN/Et3N
DMF/K2CO3
110
room temp.
40
110
45
35
35
53
2b l
2b l
3a H
skii and T. A. Prikhod’ko, Izv. Akad. Nauk SSSR, Ser. Khim., 1982,
2524; (c) T. A. Prikhod’ko, S. F. Vasilevskii and M. S. Shvartsberg,
Izv. Akad. Nauk SSSR, Ser. Khim., 1984, 2383; (d) D. L. Tarshits,
N. M. Przhiyalgovskaya and N. N. Suvorov, Khim. Geterotsikl.
Soedin., 1988, 1472; (e) T. A. Prikhod’ko, V. M. Kurilenko, Kh. N.
Khlihenko, S. F. Vasilevskii and M. S. Shvartsberg, Izv. Akad. Nauk
SSSR, Ser. Khim., 1990, 134; ( f ) M. G. Saulnier, D. B. Frennesson,
M. S. Deshpande and D. M. Vyas, Tetrahedron Lett., 1995, 36, 7841;
(g) G. Palmisano and M. Santagostino, Helv. Chim. Acta, 1993, 76,
2356; (h) A. Furstner, A. Ernst, H. Krause and A. Ptock, Tetra-
hedron, 1996, 52, 7329.
4 Methyl 3-bromopropynoate 3b was efficiently prepared by reaction
of the corresponding propiolic ester with NBS in acetone and
AgNO3 as catalyst. J. Leroy, Synth. Commun., 1992, 567.
5 G. Palmisano and M. Santagostino, Synlett, 1993, 771.
6 Palladium catalyzed synthesis of aryl, heterocyclic and vinyl
acetylene derivatives were previously reported: (a) L. Cassar,
J. Organomet. Chem., 1975, 93, 253; (b) H. A. Dieck and F. R. Heck,
J. Organomet. Chem., 1975, 93, 259. See also ref. 3(g).
BuLi (0.109 ml, 0.17 mmol, 1.6 M solution) was added drop-
wise. The mixture was stirred for 1 h. A solution of ZnCl2
(24 mg, 0.18 mmol), previously dried by melting under vacuum,
in THF (0.6 ml) was added slowly. The mixture was then stirred
for 1 h at 0 ЊC. A solution of 2-iodo-N-SEM-indole (67 mg,
0.18 mmol) and Pd(PPh3)4 (17 mg, 0.015 mmol) in THF
(0.4 ml) was added. The mixture was stirred at room tem-
perature for 24 h. It was then poured into aqueous NH4Cl
and extracted with AcOEt. The product was isolated by flash
chromatography. Yield: 35%.
Method C. 2-Iodo-N-SEM-indole (460 mg, 1.2 mmol) was
dissolved in CH3CN (10 ml). CuI (10 mg, 0.053 mmol),
Pd(PPh3)4 (32 mg, 0.028 mmol), methyl propiolate (0.12 ml, 1.4
mmol) and Et3N (1.5 ml) were added. The solution was stirred
for 6 h at 40 ЊC and for 12 h at room temperature. The mixture
was poured into a saturated NaCl solution and extracted with
AcOEt. The product was isolated by flash chromatography
Yield: 35%.
7 The required zinc chloride derivative 5c was prepared by lithium–
zinc transmetallation of the corresponding lithium derivative
generated in THF at Ϫ78 ЊC with BuLi.
8 (a) M. Kotora and E. Negishi, Synthesis, 1997, 121; (b) N. Yoneda,
S. Matsuoka, N. Miyaura, T. Fukuhara and A. Suzuki, Bull. Chem.
Soc. Jpn., 1990, 63, 212.
Method D. CuI (15 mg, 0.073 mmol), PPh3 (28 mg, 0.11
mmol) and K2CO3 (220 mg, 1.7 mmol) were dissolved in DMF
(6 ml). Methyl propiolate (0.15 ml, 1.7 mmol) and a solution of
2-iodo-N-SEM-indole (400 mg, 1.1 mmol) in DMF (4 ml) was
added. The mixture was warmed at 110 ЊC and stirred for 36 h.
The mixture was poured into brine and extracted with Et2O.
After flash chromatography purification (CH2Cl2–hexane 1:1) 1
was obtained in 53% yield. Yellow oil, Rf 0.44 (hexane–AcOEt
15:1). IR (CHCl3)/cmϪ1 3060, 2200, 1700, 1250; 1H-NMR
(CDCl3) δ 7.65 (1H, d), 7.50 (1H, d), 7.35 (1H, t), 7.20 (1H, t),
7.10 (1H, s), 5.70 (2H, s), 3.80 (3H, s), 3.55 (2H, t), 0.90 (2H, t),
0.00 (9H, s). 13C-NMR (CDCl3) δ 154.1, 137.7, 127.1, 125.3,
121.7, 121.5, 118.1, 114.1, 110.7, 87.4, 78.7, 73.1, 65.9, 52.7,
17.6, Ϫ1.6 (3C); Anal. Calcd for C18H23NO3Si: C 65.62, H 7.04,
N 4.25. Found: C 65.70, H 7.11, N 4.31%.
9 The same reaction with 2-iodo-1-PMBS-indole2 (PMBS = p-
methoxyphenylsulfonyl) gave methyl [N-(p-methoxyphenylsulfonyl)-
indol-2-yl]propiolate in 40% yield as a yellow oil. Rf 0.25 (hexane–
Et2O 1:1). 1H-NMR (CDCl3) δ 8.25 (1H, d), 7.95 (2H, AAЈ part of
AAЈBBЈ system), 7.50 (1H, d), 7.45 (1H, t), 7.25 (1H, t), 7.15 (1H, s),
6.90 (2H, BBЈ part of AAЈBBЈ system), 3.90 (3H, s), 3.80 (3H, s).
13C-NMR (CDCl3) δ 164.5, 163.1, 138.5, 135.1 (2C), 134.2, 132.1,
129.9, 127.8, 127.0, 124.1, 121.8, 114.7, 114.5 (2C), 76.6, 68.5, 55.7,
52.9; Anal. Calcd for C19H15NO5S: C 61.78, H 4.10, N 3.79. Found:
C 61.83, H 4.22, N 3.87%.
10 (a) R. D. Stephans and C. E. Castro, J. Org. Chem., 1963, 28, 3313;
(b) J. Burdon, P. L. Coe, C. R. March and J. C. Tatlow, Chem.
Commun., 1967, 1259.
11 (a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett.,
1975, 4467; (b) S. Takahashi, Y. Kuroyama, K. Sonogashira and
N. Hagihara, Synthesis, 1980, 627; (c) R. Rossi, A. Carpita and
F. Bellina, Org. Prep. Proced. Int., 1995, 27, 129. The Sonogashira
reaction has been applied also to the synthesis of indol-2-yl-
acetylenes: see ref. 2(b),(e).
Acknowledgements
12 (a) K. Okuro, M. Furuune, M. Miura and M. Nomura, Tetrahedron
Lett., 1992, 33, 5363; (b) K. Okuro, M. Furuune, M. Enna, M.
Miura and M. Nomura, J. Org. Chem., 1993, 58, 4716.
This work was supported by Ministero dell’Educazione e della
Ricerca Scientifica e Tecnologica (MURST).
13 Suzuki et al. have demonstrated that copper() species can promote
the reaction of vinyl halides with terminal alkynes: T. Ogawa,
K. Kusume, M. Tanaka, K. Hayami and H. Suzuki, Synth. Commun.,
1989, 19, 2199.
14 T. Sakamoto, F. Shiga, A. Yasuhara, D. Uchiyama, Y. Kondo and
H. Yamanaka, Synthesis, 1992, 746.
References
1 M. Ishikura, Y. Matsuzaki, I. Agata and N. Katagiri, Tetrahedron,
1998, 54, 13929.
2 B. Danieli, G. Lesma, M. Martinelli, D. Passarella, I. Peretto and
A. Silvani, Tetrahedron, 1998, 54, 14081.
3 Precedent synthesis of indol-2-ylacetylene derivatives: (a) T. A.
Prikhod’ko, Z. P. Trotsenko and S. F. Vasilevskii, Izv. Akad. Nauk
SSSR, Ser. Khim., 1980, 1690; (b) M. S. Shvartsberg, S. F. Vasilev-
15 C. Bigogno, B. Danieli, G. Lesma and D. Passarella, Heterocycles,
1995, 41, 973.
Communication 9/06023E
2670
J. Chem. Soc., Perkin Trans. 1, 1999, 2669–2670