derivatives having a substituent at the 3-position of the indole
nucleus in good yield. Although this internal alkyne protocol
affords a highly efficient method for the preparation of
3-substituted tricyclic indole skeletons4 such as mitomycins,5,6
the efficiency of the tungsten catalyst was moderate and a
stoichiometric amount of W(CO)6 was necessary to bring
the reaction to completion. Thus, it is strongly desired to
develop highly efficient catalytic reactions employable for
the substrates containing an internal alkyne moiety. In this
paper, the excellent catalytic activity of third-row transition-
metal complexes such as Pt(II) and Au(III) for the generation
and reaction of metal-containing azomethine ylides derived
from N-(o-alkynylphenyl)imine derivatives containing an
internal alkyne moiety is described.
Since a number of high-valent, late transition-metal
complexes were found to be efficient catalysts for electro-
philic activation of alkynes in the past decade,7 we initially
investigated the reaction of an imine derivative 1a having
an n-propyl group on the alkyne terminus with tert-butyl
vinyl ether 5 in toluene by the use of such metal complexes
instead of tungsten carbonyl, and the results are summarized
in Table 1. Interestingly, various metal complexes such as
higher catalytic activity than the tungsten carbonyl complex,
and in particular, PtCl2 and AuBr3 were found to be the best
catalysts in terms of product yield and reaction time,
respectively. The same mechanism as that for W(CO)5, as
depicted in Scheme 1, is proposed for these reactions.
Electrophilic activation of the internal alkyne moiety by these
metals induces the nucleophilic, 5-endo mode of cyclization
of the imino nitrogen onto the alkyne moiety to generate
the corresponding metal-containing azomethine ylides 2.
Successive [3+2] cycloaddition and 1,2-alkyl migration give
tricyclic indole with regeneration of the catalyst. On the
contrary, molybdenum carbonyl gave the desired product 4a
in low yield and, except for Pd(II), the reactions with some
other second-row transition-metal complexes such as RuCl3,
Ru3(CO)12/hν, and RhCl3 were rather sluggish. In addition,
catalytic activities of Pt(IV) chloride15 and Au(I)7,13,16 chloride
were lower than those of Pt(II) and Au(III), respectively.
(4) For reviews on the synthesis of indole derivatives, see: (a) Gribble,
G. W. Perkin Trans. 1 2000, 1045. (b) Cacchi, S.; Fabrizi, G. Chem. ReV.
2005, 105, 2873.
(5) (a) Galm, U.; Hager, M. H.; Van Lanen, S. G.; Ju, J.; Thorson, J. S.;
Shen, B. Chem. ReV. 2005, 105, 739. (b) Rajski, S. R.; Williams, R. M.
Chem. ReV. 1998, 98, 2723. For total synthesis of mitomycins, see: (c)
Fukuyama, T.; Yang, L. J. Am. Chem. Soc. 1987, 109, 7881. (d) Fukuyama,
T.; Yang, L. J. Am. Chem. Soc. 1989, 111, 8303. (e) Wang, Z.; Jimenez, L.
S. Tetrahedron Lett. 1996, 37, 6049 and references therein.
(6) For some recent examples of the preparation of mitosene skeletons,
see: (a) Pe´rez-Serrano, L.; Dom´ınguez, G.; Pe´rez-Castells, J. J. Org. Chem.
2004, 69, 5413. (b) Coleman, R. S.; Felpin, F.-X.; Chen, W. J. Org. Chem.
2004, 69, 7309. (c) Tsuboike, K.; Guerin, D. J.; Mennen, S. M.; Miller, S.
J. Tetrahedron 2004, 60, 7367. (d) Kim, M.; Vedejs, E. J. Org. Chem.
2004, 69, 7262 and references therein.
Table 1. Screening of Metal Complexes
(7) (a) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102, 813.
(b) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215. (c) Alonso, F.;
Beletskaya, I. P.; Yus, M. Chem. ReV. 2004, 104, 3079. (d) Echavarren, A.
M.; Nevado, C. Chem. Soc. ReV. 2004, 33, 431. (e) Beller, M.; Seayad, J.;
Tillack, A.; Jiao, H. Angew. Chem., Int. Ed. 2004, 43, 3368. (f) Bruneau,
C. Angew. Chem., Int. Ed. 2005, 44, 2328.
entry
catalyst
X/mol % time/h yield/% (cis:trans)
(8) (a) Kusama, H.; Yamabe, H.; Onizawa, Y.; Hoshino, T.; Iwasawa,
N. Angew. Chem., Int. Ed. 2005, 44, 468. (b) Ouh, L. L.; Mu¨ller, T. E.;
Yan, Y. K. J. Organomet. Chem. 2005, 690, 3774. (c) Hua, R.; Tian, X. J.
Org. Chem. 2004, 69, 5782. (d) Kuninobu, Y.; Kawata, A.; Takai, K. Org.
Lett. 2005, 7, 4823.
(9) (a) Chatani, N.; Inoue, H.; Morimoto, T.; Muto, T.; Murai, S. J. Org.
Chem. 2001, 66, 4433. (b) Genin, E.; Antoniotti, S.; Michelet, V.; Geneˆt,
J.-P. Angew. Chem., Int. Ed. 2005, 44, 4949. (c) Shibata, T.; Kobayashi,
Y.; Maekawa, S.; Toshida, N.; Takagi, K. Tetrahedron 2005, 61, 9018.
(10) (a) Zeni, G.; Larock, R. C. Chem. ReV. 2004, 104, 2285. (b) Muzart,
J. Tetrahedron 2005, 61, 5955.
1
2
3
4
5a
6
7
8
9
10a
11a
Mo(CO)6/hν
Re(CO)5Cl/hν
[IrCl(cod)]2
PdCl2(CH3CN)2
PtCl2
PtCl4
AuCl
AuCl3
AuBr3
100
10
5
16
5.5
26
2
9.5
25
29
1.2
0.5
13
22
15
70
73
71
90
57
49
82
70
76
33
(21:79)
(64:36)
(19:81)
(54:46)
(58:42)
(49:51)
(55:45)
(57:43)
(53:47)
(22:78)
(17:83)
11
10
10
10
10
10
100
10
(11) Pioneering studies on PtCl2-catalyzed cycloisomerization of
enynes: (a) Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J. Am. Chem.
Soc. 1994, 116, 6049. (b) Chatani, N.; Furukawa, N.; Sakurai, H.; Murai,
S. Organometallics 1996, 15, 901.
W(CO)6/hν
a 10 equiv of vinyl ether was used.
(12) For recent examples of electrophilic alkyne activation by a Pt(II)
complex, see: (a) Mainetti, E.; Mourie`s, V.; Fensterbank, L.; Malacria,
M.; Marco-Contelles, J. Angew. Chem., Int. Ed. 2002, 41, 2132. (b) Shimada,
T.; Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 10546. (c)
Bajracharya, G. B.; Nakamura, I.; Yamamoto, Y. J. Org. Chem. 2005, 70,
892. (d) Nevado, C.; Echavarren, A. M. Chem.-Eur. J. 2005, 11, 3155.
(e) Fu¨rstner, A.; Davies, P. W.; Gress, T. J. Am. Chem. Soc. 2005, 127,
8244. (f) Bhanu Prasad, B. A.; Yoshimoto, F. K.; Sarpong, R. J. Am. Chem.
Soc. 2005, 127, 12468. (g) Nakamura, I.; Mizushima, Y.; Yamamoto, Y. J.
Am. Chem. Soc. 2005, 127, 15022. (h) Fu¨rstner, A.; Davies, P. W. J. Am.
Chem. Soc. 2005, 127, 15024.
Re(I),8 Ir(I),9 Pd(II),10 Pt(II),7,11,12 and Au(III)13,14 are found
to catalyze this reaction efficiently, giving the same product
4a as that obtained by the tungsten-promoted reaction2a in
good to excellent yield. These metal complexes exhibit much
(3) For other examples of the 1,2-alkyl migration of transition-metal
carbene intermediates, see: (a) Do¨rwald, F. Z. Metal Carbenes in Organic
Synthesis; Wiley-VCH: Weinheim, Germany, 1999; p 193. (b) Zora, M.;
Herndon, J. W.; Li, Y.; Rossi, J. Tetrahedron 2001, 57, 5097 and references
therein. (c) Nagao, K.; Chiba, M.; Kim, S.-W. Synthesis 1983, 197. (d)
Bly, R. S.; Bly, R. K.; Hossain, M. M.; Lebioda, L.; Raja, M. J. Am. Chem.
Soc. 1988, 110, 7723. (e) Jiang, N.; Ma, Z.; Qu, Z.; Xing, X.; Xie, L.;
Wang, J. J. Org. Chem. 2003, 68, 893. (f) Zhang, L.; Kozmin, S. A. J. Am.
Chem. Soc. 2004, 126, 11806. (g) Lian, J.-J.; Odedra, A.; Wu, C.-J.; Liu,
R.-S. J. Am. Chem. Soc. 2005, 127, 4186.
(13) For reviews on gold-catalyzed reactions, see: (a) Hashmi, A. S. K.
Gold Bull. 2003, 36, 3. (b) Hashmi, A. S. K. Gold Bull. 2004, 37, 51.
(14) For recent examples of electrophilic alkyne activation by a Au(III)
complex, see: (a) Alfonsi, M.; Arcadi, A.; Aschi, M.; Bianchi, G.; Marinelli,
F. J. Org. Chem. 2005, 70, 2265. (b) Hashmi, A. S. K.; Rudolph, M.;
Weyrauch, J. P.; Wo¨lfle, M.; Frey, W.; Bats, J. W. Angew. Chem., Int. Ed.
2005, 44, 2798. (c) Hashmi, A. S. K.; Grundl, L. Tetrahedron 2005, 61,
6231. (d) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005, 127, 6962.
(e) Antoniotti, S.; Genin, E.; Michelet, V.; Gene´t, J.-P. J. Am. Chem. Soc.
2005, 127, 9976.
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Org. Lett., Vol. 8, No. 2, 2006