also reported Friedel-Crafts acylation with carboxylic acids
using InCl3 and Me2HSiCl,5 which proceeded under mild
conditions without the assistance of fluorinated acid anhydrides.
However, this system requires a loading of at least 30 mol %
of InCl3 to obtain satisfactory results because of decomposition
of InCl3 by an acidic proton of carboxylic acids. In addition,
only aromatic ethers such as anisole were applicable. For the
solution of this problem, we focused on esters, which had no
acidic proton and were more stable, less expensive, and easier
to handle than conventional acylating reagents such as acid
chlorides, acid anhydrides and carboxylic acids. Thus, esters
can be an idealized acylating reagent. However, this ideal
protocol remains a challenging problem because of the low
reactivity of esters. To the best of our knowledge, there are a
few practical reports of Friedel-Crafts acylation reactions with
esters. One example can be found with Olah’s report where
excess CF3SO3H was used to generate an acyl cation from
esters.6,7 Fillion reported catalytic Friedel-Crafts acylation using
Meldrum’s acid derivatives.8 However, in these systems there
were some problems such as harsh conditions, a narrow range
of substrates, and only intramolecular reaction. Herein we wish
to report the Friedel-Crafts reaction system accommodating
esters as acylation reagents, in which Me2HSiCl and only 5-10
mol % of InBr3 achieved the acylation of various arenes
including benzene and toluene.
Esters as Acylating Reagent in a Friedel-Crafts
Reaction: Indium Tribromide Catalyzed
Acylation of Arenes Using Dimethylchlorosilane
Yoshihiro Nishimoto, Srinivasarao Arulananda Babu,
Makoto Yasuda, and Akio Baba*
Department of Applied Chemistry and Center for Atomic and
Molecular Technologies (CAMT), Graduate School of
Engineering, Osaka UniVersity, 2-1 Yamadaoka,
Suita, Osaka 565-0871, Japan
ReceiVed August 29, 2008
We optimized the reaction conditions by treating anisole with
esters (Table 1). In all runs, ester, InBr3, and silyl compounds
were stirred at room temperature in 1,2-dichloroethane. After
2 h, anisole was added, and the resulting mixture was heated at
90 °C for 10 h. As expected, the use of ethyl benzoate resulted
in no acylation (entry 1). Gratifyingly, the use of tert-butyl
benzoate was found to give the desired ketone in a good yield
(entry 2). The regioselective acylation took place at the para
position of anisole and gave no other isomers. The use of either
Me3SiCl or Et3SiH resulted in very poor yields (entries 3 and
4), and the combination of Me3SiCl and Et3SiH was also
ineffective (entry 5). InCl3 gave a lower yield than InBr3 (entry
6), and other typical Lewis acids such as BF3 ·OEt2 and AlCl3
The Friedel-Crafts acylation of arenes with esters by
dimethylchlorosilane and 10 mol % of indium tribromide
has been achieved. The key intermediate RCOOSi(Cl)Me2
is generated from alkoxy esters with the evolution of the
corresponding alkanes. The scope of the alkoxy ester moiety
was wide: tert-butyl, benzyl, allyl, and isopropyl esters were
successful. In addition, we demonstrated the direct synthesis
of the indanone intermediate 11 of salviasperanol from ester
10.
Friedel-Crafts acylation is one of the fundamental methods
for the synthesis of aromatic ketones, which is an important
procedure in organic and industrial chemistry.1 Conventionally,
unstable and sensitive acylating reagents such as acid halides
or acid anhydrides are employed with excess amounts of strong
Lewis acids such as AlCl3. Hence, acylation using a stable and
easily accessed reagent under mild conditions is an important
subject of organic synthesis. Many chemists have investigated
the acylation of arenes with carboxylic acids. Most of these
reaction systems, however, have encountered the limitations of
very high temperatures2 or excess amounts of fluorinated acid
anhydrides.3 Some cases were limited to an intramolecular
reaction or activated arenes such as anisoles.3e,4 Recently, we
(3) For recent references, see: (a) Khodaei, M. M.; Alizadeh, A.; Nazari, E.
Tetrahedron Lett. 2007, 48, 4199–4202. (b) Matsushita, Y.; Sugamoto, K.;
Matsui, T. Tetrahedron Lett. 2004, 45, 4723–4727. (c) Firouzabadi, H.; Iranpoor,
N.; Nowrouzi, F. Tetrahedron Lett. 2003, 44, 5343–5345. (d) Ranu, B. C.; Ghosh,
K.; Jana, U. J. Org. Chem. 1996, 61, 9546–9547. (e) Suzuki, K.; Kitagawa, H.;
Mukaiyama, T. Bull. Chem. Soc. Jpn. 1993, 66, 3729–3734.
(4) (a) Yamato, T.; Hideshima, C.; Surya Prakash, G. K.; Olah, G. A. J.
Org. Chem. 1991, 56, 3955–3957. (b) Berman, E. M.; Hollis Showalter, H. D.
J. Org. Chem. 1989, 54, 5642–5644. (c) Premasagar, V.; Palaniswamy, V. A.;
Eisenbraun, E. J. J. Org. Chem. 1981, 46, 2947–2976.
(5) Babu, S. A.; Yasuda, M.; Baba, A. Org. Lett. 2007, 9, 405–408.
(6) (a) Poondra, R. R.; Fischer, P. M.; Turner, N. J. J. Org. Chem. 2004, 69,
6920–6922. (b) Gewald, K.; Calderon, O.; Schaefer, H.; Hain, U. Liebigs Ann.
Chem. 1984, 1390–1394. (c) Pinnick, H. W.; Brown, S. P.; McLean, E. A.; Zoller,
L. W., III J. Org. Chem. 1981, 46, 3758–3760.
(7) Hwang, J. P.; Surya Prakash, G. K.; Olah, G. A. Tetrahedron 2000, 56,
7199–7203.
(1) (a) Gore, P. H. In Aromatic Ketone Synthesis in Friedel-Crafts and Related
Reactions; Olah, G. A., Ed.; John Wiley & Sons Inc.: London, 1964; Vol. III,
Part 1, p 1. (b) Gore, P. H. Chem. ReV. 1955, 55, 229. (c) Heaney, H. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. II, p 733. (d) Olah, G. A. Friedel-Crafts Chemistry; Wiley:
New York, 1973.
(2) (a) Kawamura, M.; Cui, D.-M.; Shimada, S. Tetrahedron 2006, 62, 9201–
9209. (b) Cui, D.-M.; Zhang, C.; Kawamura, M.; Shimada, S. Tetrahedron Lett.
2004, 45, 1741–1745.
(8) (a) Fillion, E.; Dumas, A. M. J. Org. Chem. 2008, 73, 2920–2923. (b)
Fillion, E.; Dumas, A. M.; Hogg, S. A. J. Org. Chem. 2006, 71, 9899–9902. (c)
Fillion, E.; Dumas, A. M.; Kuropatwa, B. A.; Malhotra, N. R.; Sitler, T. C. J.
Org. Chem. 2006, 71, 409–412. (d) Fillion, E.; Wilsily, A. J. Am. Chem. Soc.
2006, 128, 2774–2775. (e) Fillion, E.; Fishlock, D. J. Am. Chem. Soc. 2005,
127, 13144–13145. (f) Fillion, E.; Fishlock, D.; Wilsily, A.; Goll, J. M. J. Org.
Chem. 2005, 70, 1316–1327. (g) Fillion, E.; Fishlock, D. Org. Lett. 2003, 5,
4653–4656.
10.1021/jo801914x CCC: $40.75
Published on Web 11/13/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 9465–9468 9465