Fillion et al.
Crafts reactions would be facilitated by the availability
of a moisture-stable, highly electrophilic precursor20 that
is easily prepared, functionalized, and purified, preferably
by recrystallization. Such a precursor should ideally
provide aromatic ketones catalytically at moderate tem-
peratures while generating only volatile and inert side
products. This acylating agent should be sufficiently
flexible for the facile and expedient modification and
assembly of diverse polycyclic ring systems.
vated by a Lewis acid.30 A survey of the literature on
intramolecular Lewis acid-promoted Friedel-Crafts acyl-
ation with esters provided two examples.31 Pinnick and
co-workers reported a tandem Friedel-Crafts alkylation/
acylation of benzene with ethyl cyclopropanecarboxylate
promoted by excess AlCl3 at 80 °C to yield 2-methyl-1-
indanone in 93% yield.32 Gewald’s group described the
formation of 4-oxo-3-(1,4-dihydro-3-cinnoline)carbonitrile
in 64% yield from ethyl 2-cyano-2-(2-phenylhydrazono)-
acetate and excess AlCl3 at reflux in chlorobenzene.33
In our hands, the application of Pinnick’s and Gewald’s
work to a catalytic Friedel-Crafts acylation protocol with
esters for the preparation of 1-indanones was unfruitful.
The methyl ester 1,34 bearing an electron-rich π-nucleo-
phile,35 was treated with a catalytic amount of BF3‚OEt2.
The formation of indanone 2 with only 10% conversion
directly reflected the quantity of Lewis acid used and the
stoichiometric nature of the process (Scheme 1). Since
the primary objective was to devise a catalytic acylation
reaction, metal trifluoromethanesulfonate catalysts were
examined. Ester 1 was treated with Mg(OTf)2 but the
starting material was quantitatively recovered after 24
h at reflux in CH3NO2. Mono- and dialkylated malonates
336 and 4 were inert in the presence of Sc(OTf)3, and it
was therefore concluded that methyl esters held little
promise in metal-catalyzed intramolecular Friedel-
Crafts acylation reactions. Efforts were then focused on
the development of a potent electrophile for these reaction
conditions.
Ketenes,21 isocyanates,22 isothiocyanates,23 â-lactams,24
cyclic anhydrides,25 azalactones,26 carbamates,27 and
nitriles28 have been exploited as electrophiles in intramo-
lecular Friedel-Crafts acylations but with limited suc-
cess and/or lack of generality. Esters and lactones have
attracted little attention as acylating agents due to the
predominant Friedel-Crafts alkylation pathway,29 the
carboxylate being an excellent leaving group when acti-
(20) For a review on superelectrophiles, see: Olah, G. A. Angew.
Chem., Int. Ed. Engl. 1993, 32, 767-788.
(21) (a) Intramolecular arylation of ketenium ions, see: Zhang, L.;
Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 10204-10205. (b)
Intramolecular Friedel-Crafts acylation with chromium-carbene
complex derived ketenes catalyzed by ZnCl2, see: Bueno, A. B.; Moser,
W. H.; Hegedus, L. S. J. Org. Chem. 1998, 63, 1462-1466.
(22) Intramolecular acylation with isocyanates, see: (a) Bala´zs, L.;
Nyerges, M.; Ka´das, I.; To¨ke, L. Synthesis 1995, 1373-1375. (b)
Umezawa, B.; Hoshino, O.; Sawaki, S.; Mori, K. Chem. Pharm. Bull.
1980, 28, 1003-1005. (c) Tanaka, H.; Nagai, Y.; Irie, H.; Uyeo, S.;
Kuno, A. J. Chem. Soc., Perkin Trans. 1 1979, 874-878. (d) Umezawa,
B.; Hoshino, O.; Sawaki, S.; Sashida, H.; Mori, K. Heterocycles 1979,
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W. J. Chem. Soc., Perkin Trans. 1 1978, 180-184. (f) Ohta, S.; Kimoto,
S. Chem. Pharm. Bull. 1976, 24, 2969-2976. (g) Tsuda, Y.; Isobe, K.;
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Crow and McNab reported that Meldrum’s acid (2,2-
dimethyl-1,3-dioxane-4,6-dione) could act as an electro-
phile in Friedel-Crafts acylation; flash vacuum pyrolysis
(23) Intramolecular acylation with isothiocyanates, see: (a) Smith,
P. A. S.; Kan, R. O. J. Org. Chem. 1964, 29, 2261-2265. (b) Smith, P.
A. S.; Kan, R. O. Org. Synth. 1964, 44, 91-94. (c) Smith, P. A. S.; Kan,
R. O. J. Am. Chem. Soc. 1960, 82, 4753-4754.
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1318 J. Org. Chem., Vol. 70, No. 4, 2005