ORGANIC
LETTERS
2007
Vol. 9, No. 25
5259-5262
Gold-Catalyzed Intramolecular
Carbocyclization of Alkynyl Ketones
Leading to Highly Substituted Cyclic
Enones
Tienan Jin and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku UniVersity,
Sendai 980-8578, Japan
Received October 11, 2007
ABSTRACT
The reaction of the internal alkynyl ketones 1 (n
yields, whereas that of the terminal alkynyl ketones 1 (n
)
1) under the combined catalyst, AuCl3 and AgSbF6, gave the enones 2 in good to high
0) under the combined catalyst, AuCl3 and AgOTf, afforded the cyclic enones 3.
)
Coinage metal (Au, Ag, Cu) salts act as π-electrophilic Lewis
acids and activate alkynes toward nucleophilic attack,
allowing the formation of new C-C and C-heteroatom
bonds.1 The intramolecular cyclization of alkynyl-carbonyls
and -imines leads to the formation of heterocycles2 or
carbocycles3 via oxonium or iminium intermediates (eq 1).
A different type of cycloisomerization of alkynyl carbonyls
using BF3‚OEt2 or HCl catalyst was reported by Harding in
1992.4a More recently, it was reported that the Lewis acid
catalyzed or mediated intra- and intermolecular metathesis
of alkyne-aldehydes gave the corresponding enones via a
formal [2 + 2] cycloaddition and cycloreversion (eq 2).5
Although similar transformation using alkynyl ketones is
useful for constructing tetrasubstituted cyclic enones, the
Brønsted acid or Lewis acid catalyzed reactions of ketone
analogues did not give the desired products in good yields,
instead affording a mixture of products.4a Furthermore, when
(1) For recent selected reviews, see: (a) Yamamoto, Y. J. Org. Chem.
2007, 72, 7817. (b) Hashmi, A. S. K. Chem. ReV. 2007, 107, 3180. (c)
Pati, N. T.; Yamamoto, Y. ARKIVOC 2007, 5, 121. (d) Pati, N. T.;
Yamamoto, Y. ARKIVOC 2007, 5, 6.
(2) For selected recent coinage-metal-catalyzed synthesis of hetercycles,
see: (a) Hashmi, A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew.
Chem., Int. Ed. 2000, 39, 2285. (b) Kirsch, S. F.; Binder, J. T.; Lie´bert, C.;
Menz, H. Angew. Chem., Int. Ed. 2006, 45, 5878. (c) Zhang, J.; Shmalz,
H.-G. Angew. Chem., Int. Ed. 2006, 45, 6704. (d) Seregin, I. V.; Gevorgyan,
V. J. Am. Chem. Soc. 2006, 128, 12050. (e) Harrison, T, J.; Kozak, J. A.;
Corbella-Pane´, M.; Dake, G. R. J. Org. Chem. 2006, 71, 4525. (f) Yao, T.;
Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2004, 126, 11164. (g) Schwier,
T.; Sromek, A. W.; Yap, D. M. L.; Chernyak, D.; Gevorgyan, V. J. Am.
Chem. Soc. 2007, 129, 9868. (h) Patil, N. T.; Wu, H.; Yamamoto, Y. J.
Org. Chem. 2005, 70, 4531. (i) Kusama, H.; Miyashita, Y.; Takaya, J.;
Iwasawa, N. Org. Lett. 2006, 8, 289. (j) Asao, N.; Yudha, S.; Nogami, T.;
Yamamoto, Y. Angew. Chem., Int. Ed. 2005, 44, 5526.
(3) (a) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto, Y. J.
Am. Chem. Soc. 2002, 124, 12650. (b) Asao, N.; Nogami, T.; Lee, S.;
Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 10921. (c) Dyker, G.;
Hildebrandt, D.; Liu, J.; Merz, K. Angew. Chem., Int. Ed. 2003, 42, 4399.
(d) Asao, N.; Aikawa, H.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126,
7458. (e) Kim, N.; Kim, Y.; Park, W.; Sung, D.; Gupta, A. K.; Oh, C. H.
Org. Lett. 2005, 7, 5289.
(4) For alkyne ketone metathesis, see: (a) A mixture of cyclopentenyl
ketone and cyclohexenone was obtained. Harding, C. E.; King, S. L. J.
Org. Chem. 1992, 57, 883. Also see: (b) Harding, C. E.; Hanack, M.
Tetrahedron Lett. 1971, 12, 1253. (c) Balf, R. J.; Rao, B.; Weiler, L. Can.
J. Chem. 1971, 49, 3135. (d) Hanack, M.; Harding, C. E.; Derocque, J.
Chem. Ber. 1972, 105, 421. (e) Lang, G. L.; Hall, T.-W. J. Org. Chem.
1974, 39, 3819. (f) Harding, C. E.; Stanford, G. R. J. Org. Chem. 1989,
54, 3054. (g) Sisko, J.; Balog, A.; Curran, D. P. J. Org. Chem. 1992, 57,
4341. (h) Grunwell, J. R.; Wempe, M. F.; Mitchell, J. Tetrahedron Lett.
1993, 34, 7163. (i) Balog, A.; Curran, D. P. J. Org. Chem. 1995, 60, 337.
(j) Balog, A.; Geib, S. J.; Curran, D. P. J. Org. Chem. 1995, 60, 345. (k)
Wempe, M. F.; Grunwell, J. R. J. Org. Chem. 1995, 60, 2714. (l) Wempe,
M. F.; Grunwell, J. R. Tetrahedron Lett. 2000, 41, 6709. (m) Kurtz, K. C.
M.; Hsung, R. P.; Zhang, Y. Org. Lett. 2006, 8, 231.
(5) For alkyne-aldehyde metathesis, see: (a) stoichiometric use of In-
(OTf)3, intermolecular reaction: Viswanathan, G. S.; Li, C.-J. Tetrahedron
Lett. 2002, 43, 1613. (b) Catalytic use of Yb(OTf)3, intermolecular
reaction: Curini, M.; Epifano, F.; Maltese, F.; Rosati, O. Synlett 2003, 552.
(c) Catalytic use of AgSbF6, inter- and intramolecular reaction: Rhee, J.
U.; Krische, M. Org. Lett. 2005, 7, 2493.
10.1021/ol702455v CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/08/2007