pubs.acs.org/joc
3(2H)-furanone derivatives are considered to be promis-
Cationic Gold(I)-Catalyzed Intramolecular
Cyclization of γ-Hydroxyalkynones into
3(2H)-Furanones
ing pharmaceutical candidates which exhibit antitumor,3
antiproliferative,4 antiulcer,5 antiallergic,6 selective COX-2
inhibition,7 and selective MAO-B inhibition activities.8
These features have spurred continued interest in exploring
more efficient synthetic routes of the 3(2H)-furanone frame-
work.
Masahiro Egi, Kenji Azechi, Moriaki Saneto,
Kaori Shimizu, and Shuji Akai*
Traditional methods for the preparation of substituted
3(2H)-furanones have been based on the acid-catalyzed
cyclization/dehydration reaction of 1-hydroxy-2,4-dike-
tones.3,9 Various alternative methods have also been deve-
loped, including the hydrogenolysis and subsequent acidic
hydrolysis of isoxazoles,4,10 the aldol reaction of 3-silylox-
yfuranes,11 the cyclizations of 1-halo-2,4-diketones using
bases,12 and the Knoevenagel-type condensation of R-acy-
loxycarbonyl compounds.13 Recently, the transition metal-
catalyzed cyclizations for constructing substituted 3(2H)-
furanones have attracted renewed attention, such as the
Pt- or Au-catalyzed cyclization/migration of propargylic
alcohols,14 the gold-catalyzed intramolecular cyclization of
2-oxo-3-butynoates,15 and the Pd- or Hg-catalyzed cycliza-
tion of R0-hydroxyalkynones.16
School of Pharmaceutical Sciences, University of Shizuoka,
52-1, Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan
Received January 12, 2010
The 3-acyloxyfurans, equivalents of the 3(2H)-furanones,
were synthesized from the alkynyl ketones via the Cu- or Ag-
catalyzed 1,2-migration of the acyloxy group.17 However,
these known synthetic methods have some drawbacks, for
example, insufficient yields of the desired compounds, harsh
conditions, and/or the absence of an efficient and general
procedure for the preparation of the starting materials. In
The combination of (p-CF3C6H4)3PAuCl and AgOTf
generates a powerful catalyst for the intramolecular
cyclizations of readily available γ-hydroxyalkynones un-
der mild conditions. The substituted 3(2H)-furanones are
obtained in 55-94% yields. This method is also applic-
able to the preparation of 2,3-dihydro-4H-pyran-4-ones.
(5) Felman, S. W.; Jirkovsky, I.; Memoli, K. A.; Borella, L.; Wells, C.;
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1918.
The 3(2H)-furanone moiety is well established as one of
the most fundamental components observed in abundant
naturally occurring products. Representative examples are
shown in Figure 1,1 and this class of natural furanones2
display a variety of biological activities. In addition, the
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DOI: 10.1021/jo100048j
r
Published on Web 02/26/2010
J. Org. Chem. 2010, 75, 2123–2126 2123
2010 American Chemical Society