Samarium triiodide-catalyzed conjugate addition of indoles with electron-deficient olefins

Article abstract of DOI:10.1016/j.tetlet.2005.03.174

The SmI₃-catalyzed reaction of indoles with electron-deficient olefins generated the corresponding Michael adducts in high yields. The substitution on the indole nucleus occurred exclusively at the 3-position and N-alkylation products have not

Full text of DOI:10.1016/j.tetlet.2005.03.174

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3859–3862
Samarium triiodide-catalyzed conjugate addition of indoles
with electron-deficient olefins
*
Zhuang-Ping Zhan, Rui-Feng Yang and Kai Lang
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, PR China
Received 31 January 2005; revised 25 March 2005; accepted 27 March 2005
Available online 12 April 2005
3
Abstract—The SmI -catalyzed reaction of indoles with electron-deficient olefins generated the corresponding Michael adducts in
high yields. The substitution on the indole nucleus occurred exclusively at the 3-position and N-alkylation products have not been
observed.
ꢀ
2005 Elsevier Ltd. All rights reserved.
The development of new efficient synthetic methods
leading to indole derivatives continues to receive much
attention in organic synthesis because of their biological
tions, expensive reagents, low yields of products, and
complex handling. Thus, a new efficient Lewis acid
catalyst is desirable for conjugate addition of indoles
to electron-deficient olefins.
1
activities. Various indole derivatives occur in many
2
pharmacologically and biologically active compounds.
Among them 3-substituted indoles are important build-
ing blocks for the synthesis of biologically active com-
Lanthanide ions are considered ‘‘hard’’ Lewis acids and
form complexes with substantial ionic character because
of poor overlap of the contracted 4f orbitals. Conse-
quently, lanthanides preferentially coordinate to hard
bases such as oxygen donor ligands and fluoride ion.
Many lanthanides salts have been proved to be extraor-
3
pounds and natural products. Therefore, a variety of
methods have been reported for the preparations of this
4
,5
class of compounds. The simple and direct method for
the synthesis of 3-alkylated indoles involves the conju-
gate addition of indoles to a,b-unsaturated compounds
dinarily effective Lewis acids in various chemical trans-
6,7b
4
5
in the presence of either protic or Lewis acid. How-
ever, the acid-catalyzed conjugate addition of indoles re-
quires careful control of acidity to prevent side reactions
such as dimerization or polymerization. Furthermore,
many of these procedures involve strong acidic condi-
formations.
electron reducing agent has played an important role
Though samarium diiodide as a single
7
in organic synthesis, little work has been carried out
on lanthanide salt, samarium triiodide used as a Lewis
acid catalyst. This promoted us to investigate the use
R4
R2
O
O
1
0 mol% SmI3
R3
+
R3
R4
N
R1
R2
CH CN, reflux
3
N
R1
1
3
R =H, PhCH2
R =Ph, CH3, Ph CH CH
2
4
R =H, CH , Ph
R =Ph, H
3
3
4
(CH )
2 3
R =R =
Scheme 1.
Keywords: Samarium triiodide; Indole; a,b-Unsaturated compounds; Michael reaction.
*
Corresponding author. Tel.: +86 592 2180318; fax: +86 592 2185780; e-mail: zpzhan@xmu.edu.cn
0
040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.174

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Z.-P. Zhan et al. / Tetrahedron Letters 46 (2005) 3859–3862
Table 1. Conjugate addition of indoles with electron-deficient olefins
Entry
1
Nucleophile
Electrophile
Product
Time (h)
Isolated yield (%)
O
O
O
a
1
95
N
H
N
H
O
O
2
3
b
c
1
1
95
90
N
H
N
H
O
N
H
Ph
N
H
Ph
Ph
O
O
Ph
Ph
4
5
d
e
6
6
85
83
N
H
Ph
Ph
Ph
N
H
Ph
Ph
O
O
O
N
H
Ph
N
H
O
Ph
6
f
6
75
N
Ph
Ph
N
CH Ph
CH Ph
2
2
Ph
O
O
Ph
7
8
g
h
6
6
76
75
N
H
Ph
Ph
N
H
Ph
O
O
N
H
Ph
N
H
O
O
9
i
j
6
6
85
90
N
H
N
O
H
O
10
N
H
Ph
Ph
N
H
Ph
Ph
O
O
1
1
2
k
l
12
1
70
95
N
H
Ph
N
H
Ph
Ph
NO2
NO2
1
Ph
N
H
N
H
p-MeO- Ph
NO2
NO2
1
1
3
4
m
1
1
92
95
p-MeOPh
N
H
N
H
p-MeO-Ph
NO2
NO2
n
N
p-MeOPh
N
CH Ph
2
CH Ph
2

Z.-P. Zhan et al. / Tetrahedron Letters 46 (2005) 3859–3862
3861
of samarium triiodide as a Lewis acid for conjugate
addition of indoles to electron-deficient olefins. Herein,
we report the remarkable catalytic activity of samarium
triiodide in this Michael reaction (Scheme 1).
3. (a) Joule, J. A. In Science of Synthesis; Thomas, E. J., Ed.;
Thieme: Stuttgart, 2000; Vol. 10, pp 361–652; (b) Gribble,
G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045–1075; (c)
Moore, R. E.; Cheuk, C.; Yang, X. Q.; Patterson, G. M. L.;
Bonjouklian, R.; SmitKa, T. A.; Mynderse, J. S.; Foster, R.
S.; Jones, N. D.; Swartzendruber, J. K.; Deeter, J. B.
J. Org. Chem. 1987, 52, 1036–1043; (d) Garnick, R. L.;
Levery, S. B.; Lequesne, P. W. J. Org. Chem. 1978, 43,
1226–1229; (e) Moore, R. E.; Cheuk, C.; Patterson, G. M.
L. J. Am. Chem. Soc. 1984, 106, 6456–6457.
4. (a) Szmuszkovicz, J. J. Am. Chem. Soc. 1975, 79, 2819–
2821; (b) Noland, W. E.; Christensen, G. M.; Sauer, G. L.;
Dutton, G. G. S. J. Am. Chem. Soc. 1955, 77, 456–457; (c)
Iqbal, Z.; Jackson, A. H.; Rao, K. R. N. Tetrahedron Lett.
First, we carried out the reaction of indole with methyl
vinyl ketone in the presence of catalytic amount of SmI3
(
10 mol%) in acetonitrile and obtained the correspond-
ing 3-alkylated indole (product a, Table 1) in 95% yield.
Then, various a,b-unsaturated compounds were reacted
with indole, 2-methylindole, and 2-phenylindole to give
the corresponding 3-alkylated products in high yields.
8
The results are summarized in Table 1. Electron-defi-
1
988, 29, 2577–2580.
. (a) Harrington, P. E.; Kerr, M. A. Synlett 1996, 1047–1048;
b) Harrington, P.; Kerr, M. A. Can. J. Chem. 1998, 76,
256–1265; (c) Loh, T. P.; Wei, L. L. Synlett 1998, 975–976;
d) Loh, T. P.; Pei, J.; Lin, M. Chem. Commun. 1996, 2315–
316; (e) Yadav, J. S.; Abraham, S.; Reddy, B. V. S.;
cient olefins, such as methyl vinyl ketone, chalcone,
benzalacetone, cyclohexenone, and dibenzylidene ace-
tone, afforded the products in good to excellent yields.
The treatment of b-nitrostyrene with indole produced
the corresponding 3-alkylated indole in 92–95% yields
5
(
1
(
2
(
tained via InCl -catalyzed reaction, SmI was more
entries 12, 13). In comparison with 78% of product ob-
5
Sabitha, G. Synthesis 2001, 2165–2169; (f) Bandini, M.;
Cozzi, P. G.; Giacomini, M.; Melchiorre, P.; Selva, S.;
Umani-Ronchi, A. J. Org. Chem. 2002, 67, 3700–3704; (g)
Arcadi, A.; Bianchi, G.; Chiarini, M.; Anniballe, G.;
Marinelli, F. Synlett 2004, 6, 944–950; (h) Ji, S.-J.; Wang,
S.-Y. Synlett 2003, 13, 2074–2076.
e
3
3
efficient for the Michael addition of indole to b-nitrost-
yrene. Though 2-phenylindole was more hindered, its 3-
position alkylation was proceeded in good to excellent
yields (entries 3, 10, 11). The reactions were clean and
the products were obtained in high yields without the
formation of any side products such as N-alkylation
product. This important result provided a remarkable
contrast to similar reactions under palladium catalysis,
6
. (a) Evans, D. A.; Wu, J. J. Am. Chem. Soc. 2003, 125,
0162–10163; (b) Kobayashi, S.; Hamada, T.; Nagayama,
1
S.; Manabe, K. Org. Lett. 2001, 3, 165–167; (c) Sibi, M. P.;
Manyem, S. Org. Lett. 2002, 4, 2929–2932; (d) Qian, C.-T.;
Wang, L.-C. Tetrahedron 2000, 56, 7193–7197.
9
where N-alkylation was predominant. Furthermore,
7. (a) Krief, A.; Laval, A. M. Chem. Rev. 1999, 99, 745–777;
(b) Molander, G. A. Chem. Rev. 1992, 92, 29–68; (c)
Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307–
the indole nitrogen did not require prior protection
and the avoidance of strong bases for deprotection per-
mitted compatibility with a wide range of functional
groups. The procedure did not require any acidic pro-
moters or inert atmospheric condition.
3
2
38; (d) Steel, P. G. J. Chem. Soc., Perkin Trans. 1 2001,
727–2751.
8
. Typical experimental procedure: a mixture of indole
(
(
(
1 mmol) or 2-methylindole (1 mmol) or 2-phenylindole
1 mmol), electron-deficient olefin (1 mmol) and SmI
0.1 mmol) in CH CN (1 mL) was stirred at reflux condi-
3
In conclusion, samarium triiodide has been found to be
a superior Lewis acid for the alkylation of indoles with
electron-deficient olefins.
3
tion. After completion of the reaction as indicated by TLC,
the resulting mixture was diluted with H O (10 mL) and
2
extracted with EtOAc (15 mL · 3). The combined organic
layer was washed with brine and dried over anhydrous
Acknowledgement
2 4
Na SO . After removal of the solvent under reduced
pressure, the crude product was purified by column
chromatography on silica gel (eluant: EtOAc: Petroleum
ether = 1:6) to afford the corresponding 3-alkylated indole.
The financial support is provided by FuJian Provincial
Department of Science and Technology (2003J019).
1
All new compounds were fully characterized by H NMR,
C NMR, MS, IR and elemental analysis.
1
3
3
-(1-benzyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one(f): 311
À1
1
References and notes
mg (75%). IR (film) tmax: 3034, 1680, 1598, 1493 cm ; H
NMR (500 MHz, CDCl ) d = 3.72 (dd, J = 7, 16.5 Hz, 1 H),
3
1
. (a) Aubry, C.; Patel, A.; Mahale, S.; Chaudhuri, B.;
Marechal, J.-D.; Sutcliffe, M. J.; Jenkins, P. R. Tetrahedron
Lett. 2005, 46, 1423–1425; (b) Marugan, J. J.; Manthey, C.;
Anaclerio, B.; Lafrance, L.; Lu, T.; Markotan, T.; Leonard,
K. A.; Crysler, C.; Eisennagel, S.; Dasgupta, M.; Tomczuk,
B. J. Med. Chem. 2005, 48, 926–934; (c) Fukuyama, T.;
Chen, X.-Q. J. Am. Chem. Soc. 1994, 116, 3125–3126; (d)
Vaillancourt, V.; Albizati, K. F. J. Am. Chem. Soc. 1993,
3.81 (dd, J = 7, 16.5 Hz, 1H), 5.09 (t, J = 7 Hz, 1H), 5.26 (s,
2H), 6.90–7.07 (m, 4H), 7.10–7.21 (m, 3H), 7.23–7.30 (m,
5H), 7.33–7.47 (m, 5H), 7.50–7.55 (m, 1H), 7.88–7.93 (m,
1
3
3
2H); C NMR (125 MHz, CDCl ) d = 38.3, 45.3, 49.9,
109.7, 118.4, 119.1, 119.8, 121.9, 125.6, 126.3, 126.6, 127.3,
127.5, 127.8, 128.1, 128.4, 128.5, 128.7, 132.9, 137.0, 137.2,
+
137.6, 144.3, 198.6; ESI-MS: m/z (%) = 416 (88) [M+H ],
+
438 (100) [M+Na ]; Anal. Calcd for C30
H25NO: C, 86.72;
1
15, 3499–3502.
H, 6.06; N, 3.37. Found: C, 86.84; H, 6.05; N, 3.43.
3-(1-(4-methoxyphenyl)-2-nitro ethyl)-1H-indole(m): 272
mg (92%). IR (film) tmax: 3412, 3058, 1610, 1548, 1509,
2
. (a) Zhang, H.-C.; Ye, H.; Moretto, A. F.; Brumfield, K. K.;
Maryanoff, B. E. Org. Lett. 2000, 2, 89–92; (b) Faul, M. M.;
Winneroski, L. L.; Krumrich, C. A. J. Org. Chem. 1998, 63,
À1
1
3
1373 cm ; H NMR (500 MHz, CDCl ) d = 3.79 (s, 3H),
6
053–6058; (c) Bennasar, M.-L.; Vidal, B.; Bosch, J. J. Org.
4.91 (dd, J = 7.5, 12.5 Hz, 1H), 5.06 (dd, J = 7.5, 12.5 Hz,
1H), 5.15 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 8.5 Hz, 2H), 7.03
(s, 1H), 7.09 (t, J = 7.5 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H),
7.26 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 7.5 Hz, 1H), 7.45 (d,
Chem. 1997, 62, 3597–3609; (d) Tani, M.; Matsumoto, S.;
Aida, Y.; Arikawa, S.; Nakane, A.; Yokoyama, Y.;
Murakami, Y. Chem. Pharm. Bull. 1994, 42, 443–453.

3862
Z.-P. Zhan et al. / Tetrahedron Letters 46 (2005) 3859–3862
1
3
J = 7.5 Hz, 1H), 8.10 (s, 1H); C NMR (125 MHz, CDCl
d = 40.9, 55.2, 79.7, 111.3, 114.3, 114.8, 119.0, 119.9, 121.4,
22.7, 126.1, 128.8, 131.2, 136.5, 158.9; ESI-MS: m/z
3
)
(t, J = 7 Hz, 1H), 5.00 (s, 2H), 6.64–6.71 (m, 2H), 6.76–6.80
(m, 1H), 6.86–6.93 (m, 3H), 6.96–7.02 (m, 1H), 7.04–7.16
1
3
1
(m, 6H), 7.26–7.34 (m, 1H); C NMR (125 MHz, CDCl ) d
3
+
+
(
%) = 297 (15) [M+H ], 319 (100) [M+Na ]; Anal. Calcd
for C17 : C, 68.91; H, 5.44; N, 9.45. Found: C,
8.80; H, 5.32; N, 9.46.
-benzyl-3-(1-(4-methoxyphenyl)-2-nitro ethyl)-1H-indole
40.6, 49.6, 54.8, 79.5, 109.8, 113.6, 114.0, 119.0, 119.4, 122.2,
125.4, 126.4, 126.6, 127.4, 128.5, 128.6, 131.2, 136.7, 137.1,
16 2 3
H N O
+
158.6; ESI-MS: m/z (%) = 387 (100) [M+H ], 409 (91)
6
1
+
[M+Na ]; Anal. Calcd for C H N O : C, 74.59; H, 5.74;
2
4
22
2
3
(
1
4
n): 367 mg (95%). IR (film) tmax: 3027, 1606, 1548, 1501,
3
) d = 3.53 (s, 3H),
.66 (dd, J = 7, 11 Hz, 1H), 4.79 (dd, J = 7, 11 Hz, 1H), 4.93
N, 7.25. Found: C, 74.46; H, 5.73; N, 7.13.
9. Trost, B. M.; Molander, G. A. J. Am. Chem. Soc. 1981,
103, 5969–5972.
À1
1
373 cm ; H NMR (500 MHz, CDCl