Carbon-Carbon Bond Formation Reaction of Zirconacyclopentadienes with Alkynes in the Presence of Ni(II)-complexes Tamotsu Takahashi,* Fu-Yu Tsai, Yanzhong Li, Kiyohiko Nakajima, ² and Martin Kotora Contribution from the Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido UniVersity, Kita-ku, Sapporo 060-0811Japan, and CREST, Science and Technology Corporation (JST), Sapporo 060-0811, Japan ReceiVed March 8, 1999 Abstract: Zirconacyclopentadienes, prepared from two alkynes or a diyne, reacted with the alkyl-, trimethylsilyl-, or alkoxy-substituted third alkyne as well as an alkyne with an electron-withdrawing group in the presence of a stoichiometric amount of NiBr 2 (PPh 3 ) 2 to give benzene derivatives in good yields. Heteroatom-containing diynes such as dipropargylbenzylamine and propargyl-homopropargylbenzylamine gave isoindoline and tetrahydroisoquinoline derivatives in good to high yields. This procedure was also used for the selective preparation of benzene derivatives from three different alkynes. The use of trimethylsilyl-substituted alkyne as the first, second or third alkyne afforded desilylated benzene derivatives. The reaction of zirconacyclopen- tadienes with allenes gave benzene derivatives as a mixture of two isomers. Introduction Transition-metal-catalyzed or -mediated coupling of three alkynes to give benzene derivatives has been well established in organic synthesis. 1,2 Despite intense research in this area, the problem of the selective intermolecular coupling of three alkynes has remained virtually unsolved. Recently, we have reported that this problem can be overcome by the reaction of zircona- cyclopentadienes, which can be selectively prepared from two different alkynes, 3 with alkynes bearing electron-withdrawing groups in the presence of a stoichiometric amount of CuCl (eq 1). 4 This method was the first example of the one-pot formation of benzene derivatives from three different alkynes in high yields (83-95%) with excellent selectivities. 4a However, the critical limitation of this method is that at least one electron-withdrawing group is required for the third alkyne, since the major reaction step of this method is Michael addition of the dienylcopper species to the third alkyne. Therefore, consequently, an alkyne with electron-donating groups such as alkyl, trimethylsilyl, and alkoxy groups cannot be used for this reaction. One reasonable approach to overcome this difficulty is development of an insertion reaction of the third alkyne into a dienylmetal and such insertion reaction can be expected for the late transition-metal compounds such as nickel. Therefore, we have investigated a novel and general reaction system using zirconacyclopentadienes and the late transition-metal com- pounds. In this paper we would like to report a novel reaction of zirconacyclopentadienes with the third alkynes which have electron-donating groups as well as an electron-withdrawing group in the presence of Ni(II)-complexes to afford benzene derivatives (eq 2). This can be a general one-pot procedure for the selectiVe synthesis of benzene deriVatiVes by intermolecular coupling of alkynes or by intramolecular coupling of diynes. ² Department of Chemistry, Aichi University of Education, Igaya, Kariya, 448-8542, Japan, and CREST, Science and Technology Corporation (JST), Kariya 448-8542, Japan (1) (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-92. (b) Grotjahn, D. B. ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Elsevier Science Ltd: Oxford, 1995; Vol 12; pp 741-770. (c) Schore, N. E. ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds; Pergamon Press Ltd: Oxford, 1991; Vol. 5; pp 1129-1162. (d) Harrington, P. J. Transition Metals in Total Synthesis, John Wiley & Sons: New York, 1990; pp 200-240. (e) Schore, N. E. Chem. ReV. 1988, 88, 1081-1119. (f) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539-556. (2) (a) Boese, R.; Van Sickle, A. P.; Vollhardt, K. P. C. 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(4) For formation of benzene derivatives from three different alkynes via transmetalation of zirconacyclopentadienes to organocopper, see (a) Takahashi, T.; Xi, Z.; Yamazaki, A.; Liu, Y.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 1998, 120, 1672-1680. (b) Takahashi, T.; Kotora, M.; Xi, Z. J. Chem. Soc., Chem. Commun. 1995, 361-362. For other examples of transmetalations of zirconacycles to organocopper compounds, see: (c) Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N.; Nakajima, K. Organo- metallics 1994, 13, 4183-4185. (d) Kasai, K.; Kotora, M.; Suzuki, N.; Takahashi, T.; J. Chem. Soc., Chem. Commun. 1995, 109-110. (e) Takahashi, T.; Kotora, M.; Xi, Z. J. Chem. Soc., Chem. Commun. 1995, 1503-1504. (f) Takahashi, T.; Hara, R.; Nishihara, Y.; Kotora, M. J. Am. Chem. Soc. 1996, 118, 5154-5155. (g) Takahashi, T.; Xi, Z.; Kotora, M.; Xi, C.; Nakajima, K. Tetrahedron Lett. 1996, 37, 7521-7524. (h) Takahashi, T.; Nishihara, Y.; Hara, R.; Huo, S.; Kotora, M. Chem. Commun. 1997, 1599-1600. (i) Kotora, M.; Umeda, C.; Ishida, T.; Takahashi, T. Tetra- hedron Lett. 1997, 38, 8355-8358. (j) Kotora, M.; Xi, C.; Takahashi, T. Tetrahedron Lett. 1998, 39, 4321-4324. (k) Takahashi, T.; Sun, W.-H.; Liu, Y.; Nakajima, K.; Kotora, M. Organometallics 1998, 17, 3841-3843. 11093 J. Am. Chem. Soc. 1999, 121, 11093-11100 10.1021/ja990750c CCC: $18.00 © 1999 American Chemical Society Published on Web 11/19/1999