ORGANIC
LETTERS
2005
Vol. 7, No. 19
4129-4132
Unusual Gold(I)-Catalyzed Isomerization
of 3-Hydroxylated 1,5-Enynes: Highly
Substrate-Dependent Reaction Manifolds
Fabien Gagosz*
Laboratoire de Synthe`se Organique, Ecole Polytechnique, 91128 Palaiseau, France
Received June 16, 2005
ABSTRACT
The gold(I) isomerization of diversely substituted 3-hydroxylated enynes has led to the discovery of three new unreported skeletal rearrangements
furnishing structures such as alkylidene-cyclopentenes, cyclohexadienes or
r,
â
-unsaturated aldehydes under very mild conditions.
Gold(I) complexes have recently emerged as efficient and
mild catalysts for the transformation of substrates possessing
an alkyne functionality into a range of useful structural
motifs.1 The potential of such catalysts has been mostly
highlighted by various studies related to the conversion of
enynes into cycloisomerized products.2 In this respect, we
were particularly intrigued by the possibility that ring A of
the bioactive guanacastepene A3 could be synthesized using
Scheme 1. Retrosynthesis of Guanacastepene A
(1) For a review on homogeneous catalysis by gold, see: Hashmi, A. S.
K. Gold Bull. 2004, 37, 51-65.
(2) (a) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem. Soc.
2000, 122, 11553-11554. (b) Nieto-Oberhuber, C.; Lopez, S.; Echavarren,
A. M. J. Am. Chem. Soc. 2005, 127, 6178-6179. (c) Mun˜oz, M.; Adrio,
J.; Carretero, J. C.; Echavarren, A. M. Organomettalics 2005, 24, 1293-
1300. (d) Nevado, C.; Echavarren, A. M. Chem. Eur. J. 2005, 11, 3155-
3164. (e) Nieto-Oberhuber, C.; Mun˜oz, M.; Bun˜uel, E.; Nevado, C.;
Ca´rdenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402-
2406. (f) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,
5802-5803. (g) Luzung, M. R.; Markham, J. P.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 10858-10859. (h) Sherry, B. D.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 15978-15979. (i) Staben, S. T.; Kennedy-Smith, J. J.; Toste,
F. D. Angew. Chem., Int. Ed. 2004, 43, 5350-5352. (j) Kennedy-Smith, J.
J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 4526-4527.
(k) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 11806-11807.
(l) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005, 127, 6962-6963.
(3) Brady, S. F.; Singh, M. P.; Janso, J.; E.; Clardy, J. J. Am. Chem.
Soc. 2000, 122, 2116-2117.
a gold(I)-catalyzed cycloisomerization of a well defined
enyne (Scheme 1). Actually, this approach would allow the
early introduction of most of the functionalities present on
ring A, while the presence of the cyclopropyl ring could serve
as a springboard for the construction of ring B. We herein
report results concerning these studies that led to the
discovery of three new unusual gold(I)-catalyzed isomer-
izations of 3-hydroxylated 1,5-enynes.4
10.1021/ol051397k CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/18/2005