Synthesis of Indenes via Palladium-Catalyzed Carboannulation of Diethyl 2-(2-(1-alkynyl)phenyl)malonate and Organic Halides
SCHEME 1
Li-Na Guo,† Xin-Hua Duan,† Hai-Peng Bi,† Xue-Yuan Liu,† and Yong-Min Liang*,†,‡
SCHEME 2
State Key Laboratory of Applied Organic Chemistry, Lanzhou UniVersity, and State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000, People’s Republic of China
[email protected] ReceiVed January 21, 2006
Highly substituted indenes have been prepared in good yields by the palladium-catalyzed carboannulation of diethyl 2-(2(1-alkynyl)phenyl)malonate with aryl, benzylic, and alkenyl halides. The reaction conditions and the scope of the process were examined, and a possible mechanism is proposed. Indene derivatives, in particular, multiply-substituted ones, have been attractive, and synthetically useful methods for their synthesis have been developed.1 Among the most important synthetic routes to such compounds are reduction/dehydration of indanones,2 the cyclization of phenyl-substituted allylic alcohols,3 and the ring expansion of substituted cyclopropenes.4 Recently, Gridnev et al. and Yamamoto et al. have reported Pd-catalyzed or Pt-catalyzed intramolecular carbalkoxylation reactions accompanied by an unprecedented 1,2-alkyl migration to the synthesis of functionalized indenes.5 Very recently, Larock et al. have reported a convenient method for the preparation of * Corresponding author. Fax: +86-931-8912582. Tel.: +86-931-8912593. † Lanzhou University. ‡ Chinese Academy of Science.
(1) (a) Xi, Z.; Guo, R.; Mito, S.; Yan, H.; Kanno, K.-i.; Nakajima, K.; Takahashi, T. J. Org. Chem. 2003, 68, 1252 and references therein. (b) Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 7280. (c) Lautens, M.; Marquardt, T. J. Org. Chem. 2004, 69, 4607. (d) Chang, K.-J.; Rayabarapu, D. K.; Cheng, C.-H. J. Org. Chem. 2004, 69, 4781. (2) (a) Prough, J.; Alberts, A.; Deanna, A.; Gilfillian, J.; Huff, R.; Smith, J.; Wiggins, J. J. Med. Chem. 1990, 33, 758. (b) Ikeda, S.; Chatani, N.; Kajikawa, Y.; Ohe, K.; Murai, S. J. Org. Chem. 1992, 57, 2. (c) Becker, C.; McLaughlin, M. Synlett 1991, 642. (3) Miller, W.; Pittman, C. J. Org. Chem. 1974, 39, 1955. (4) Yoshida, H.; Kato, M.; Ogata, T. J. Org. Chem. 1985, 50, 1145. (5) (a) Nakamura, I.; Bajracharya, G. B.; Wu, H.; Oishi, K.; Mizushima, Y.; Gridnev, I. D.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 15423. (b) Nakamura, I.; Bajracharya, G. B.; Mizushima, Y.; Yamamoto, Y. Angew. Chem., Int. Ed. 2002, 41, 4328.
indenes by the palladium-catalyzed carboannulation of internal alkynes with functionally substituted aryl halides (Scheme 1).6 The transition-metal-catalyzed cyclization of alkynes, which possess nucleophilic centers in close proximity to the carboncarbon triple bond, by in situ coupling/cyclization reactions,7 and reactions promoted by vinylic, aryl, and alkynylpalladium complexes,8 have also been shown to be extremely effective for the synthesis of a wide variety of carbo- and heterocycles. In our own laboratories, it has been demonstrated that palladiumcatalyzed annulation can be effectively employed for the synthesis of furans.9 Herein, we wish to report that the palladium-catalyzed annulation of diethyl 2-(2-(1-alkynyl)phenyl)malonate and a variety of organic halides offers an efficient, direct route to highly substituted indenes (Scheme 2). We started out our investigation of the reaction conditions by using 1.0 equiv of diethyl 2-(2-(2-phenylethynyl)phenyl)malonate (1a; 0.2 mmol), 1.2 equiv of iodobenzene, 5 mol % of Pd2(dba)3 as the catalyst, and 2.0 equiv of K2CO3 in DMF as the solvent at 100 °C for 16 h under argon. The desired product, diethyl 2,3-diphenyl-1H-indene-1,1-dicarboxylate (3aa) was isolated in 36% yield. While using Pd(PPh3)4 as the catalyst, the reaction afforded 3aa in 71% yield. We then screened various bases using 1a and iodobenzene as the reactants and Pd(PPh3)4 as the catalyst in DMF (Table 1). We found that K2CO3 was the most effective base (Table 1, entry 5). The use of other inorganic bases such as K3PO4, KOAc, Cs2CO3, and KOtBu failed to improve the yield of 3aa (Table 1, entries 3, 4, 6, and 7). Triethylamine and tri-n-butylamine were ineffective (Table 1, entries 1 and 2). The optimum reaction conditions thus far developed employ 1.0 equiv of 1a, 1.2 equiv of the (6) Zhang, D.; Yum, E. K.; Liu, Z.; Larock, R. C. Org. Lett. 2005, 7, 4963. (7) For reviews, see: (a) Cacchi, S.; Fabrizi, G. Chem. ReV. 2005, 105, 2873. (b) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. ReV. 2004, 104, 3079. For some recent examples, see: (c) Harmata, M.; Rayanil, K.-o.; Gomes, M. G.; Zheng, P.; Calkins, N. L.; Kim, S.-Y.; Fan, Y.; Bumbu, V.; Lee, D. R.; Wacharasindhu, S.; Hong, X. Org. Lett. 2005, 7, 143. (d) Roesch, K. R.; Larock, R. C. Org. Lett. 1999, 1, 553. (e) Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86. (f) Zhang, H.; Larock, R. C. Org. Lett. 2001, 3, 3083. (g) Zhang, H.; Larock, R. C. J. Org. Chem. 2002, 67, 7048. (h) Kundu, N. G.; Khan, M. W. Tetrahedron. 2000, 56, 4777. (8) For reviews, see: (a) Zeni, G.; Larock, R. C. Chem. ReV. 2004, 104, 2285. (b) Cacchi, S. J. Organomet. Chem. 1999, 576, 42 and references therein. For some recent examples, see: (c) Bossharth, E.; Desbordes, P.; Monteiro, N.; Balme, G. Org. Lett. 2003, 5, 2441. (d) Dai, G.; Larock, R. C. Org. Lett. 2001, 3, 4035. (e) Dai, G.; Larock, R. C. J. Org. Chem. 2003, 68, 920. (f) Wei, L.-M.; Lin, C.-F.; Wu, M.-J. Tetrahedron Lett. 2000, 41, 1215. (9) Duan, X.-h.; Liu, X.-y.; Guo, L.-n.; Liao, M.-c.; Liu, W.-M.; Liang, Y.-m. J. Org. Chem. 2005, 70, 6980.
10.1021/jo0601361 CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/15/2006
J. Org. Chem. 2006, 71, 3325-3327
3325
TABLE 1. Effect of Base on the Reaction of 1a with Iodobenzenea entry
base
isolated yield of 3aab (%)
1 2 3 4 5 6 7
Et3N (n-Bu)3N K3PO4 KOAc K2CO3 Cs2CO3 KOt-Bu
no reaction no reaction 15 (
