Efficient aromatic and heteroatom acylations using catalytic indium complexes with lithium perchlorate

Article abstract of DOI:10.1016/S0040-4039(00)02122-5

The combination of an indium complex with lithium perchlorate affords a potent system for the catalytic acylation of electron-rich aromatics and alcohols. The use of isopropenyl acetate as acyl donor results in cleaner methodology with acetone as the only by-product. The study has also revealed an indium-catalysed ketalisation reaction.

Full text of DOI:10.1016/S0040-4039(00)02122-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 773–775
Efficient aromatic and heteroatom acylations using catalytic
indium complexes with lithium perchlorate
Christopher J. Chapman,a Christopher G. Frost,a,* Joseph P. Hartleya and Alan J. Whittleb
aDepartment of Chemistry, University of Bath, Bath BA2 7AY, UK
bZeneca Agrochemicals, Jealott’s Hill International Research Centre, Bracknell, Berkshire RG42 6ET, UK
Received 11 September 2000; accepted 20 November 2000
Abstract—The combination of an indium complex with lithium perchlorate affords a potent system for the catalytic acylation of
electron-rich aromatics and alcohols. The use of isopropenyl acetate as acyl donor results in cleaner methodology with acetone
as the only by-product. The study has also revealed an indium-catalysed ketalisation reaction. © 2001 Elsevier Science Ltd. All
rights reserved.
desirable to maintain this level of activity to reduce
problems associated with catalyst removal and product
purification, we therefore focussed on developing condi-
tions that required the use of only 1 mol% of the
indium catalyst. The acylation reaction of anisole 1
with acetic anhydride to afford product 2 was investi-
gated to identify the optimum catalyst and solvent
combination (Scheme 1).
The catalytic Friedel–Crafts acylation reaction pro-
vides a practical alternative for the synthesis of aro-
matic ketones avoiding the use of stoichiometric
promoters such as aluminium trichloride.1 The most
effective systems to emerge have employed lan-
thanide(III) perfluoroalkylsulfonates,2 (perfluoroalkyl-
sulfonyl)amides3 and (perfluoroalkylsulfonyl)methides4
as Lewis acid catalysts. The use of robust indium(III)
complexes as efficient Lewis acids is becoming increas-
ingly widespread in catalytic organic synthesis, for
example Diels–Alder reactions,5 Michael additions,6
Mukaiyama-aldol reactions7 and glycosylations.8 In this
report, an efficacious catalyst system is presented for
the Friedel–Crafts acylation of aromatics and het-
eroatom acylations which employs low loadings of the
active indium(III) complex.
As evidenced in Table 1, the reaction was sensitive to
variations in the catalyst, additive and solvent combina-
tions. Other solvents were tried including water,
dichloromethane, nitrobenzene, ethyl acetate and acetic
anhydride but all proved less effective than ni-
tromethane. The type of anionic ligand employed is
confirmed to be critical to obtaining a high yield in the
In previous work we have demonstrated that indiu-
m(III) triflate functions as an efficient Lewis acid cata-
lyst at very low catalyst loadings (0.5–1 mol%).9 It is
Table 1. The acylation of anisole
Entry Catalyst
Additive
Solvent Yield (%)
1
2
3
4
5
6
7
8
InCl3
–
–
–
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeNO2
MeNO2
25
28
57
7
55
82
40
79
88
96
In(OTf)3
In(ClO4)3·8H2O
InCl3
InCl3
InCl3
In(OTf)3
In(OTf)3
In(OTf)3
In(OTf)3
–
3 mol% AgSbF6
3 mol% AgBF6
3 mol% AgClO4
4 mol% LiClO4
4 mol% LiClO4
25 mol% LiClO4
100 mol% LiClO4 MeNO2
100 mol% LiClO4 MeNO2
100 mol% LiClO4 MeNO2
9
10
11
12
<5
Scheme 1.
In(OTf)3
99a
* Corresponding author.
a Reaction was conducted at room temperature for 40 hours.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02122-5

774
C. J. Chapman et al. / Tetrahedron Letters 42 (2001) 773–775
Scheme 2.
Scheme 3.
catalytic Friedel–Crafts process.10 The use of perchlo-
rate as counterion (entry 6) or the use of lithium
perchlorate as an additive provided the most active
system. In the absence of indium catalyst the lithium
perchlorate did not promote the illustrated reaction
(entry 11). The acceleration of the Friedel–Crafts acyl-
ation reaction in the presence of lithium perchlorate
has been noted with other catalysts and is reported to
be due to the formation of a reactive cationic species
when combined with the acyl donor.11 The efficiency
of this unique catalyst system is demonstrated by the
room temperature synthesis of ketone 2 using only 1
mol% of indium(III) triflate (entry 12).
tions outlined in Scheme 3. A typical example is the
extremely efficient acylation of benzyl alcohol 8 to
furnish benzyl acetate 9 in quantitative yield. Whilst
attempting the diacylation of 1-phenyl-1,2-ethanediol
10 we noted the formation of 12 in significant yield
along with the expected product 11. It appeared that
the acetone generated in situ from the acylation pro-
cess was being consumed in a competitive ketalisation
reaction of 10. Given that Lewis acids are known to
promote such transformations the diol 10 was inde-
pendently reacted with acetone (1.1 equiv.) to reveal
an efficient indium-catalysed ketalisation process
(Scheme 4).13
The present catalyst system is highly effective for the
acylation of anisole and other electron-rich aromatics
such as mesitylene, m-xylene and furan to afford
products 3, 4 and 6 (Scheme 2). It was less effective
with toluene which required 10 mol% of indium cata-
lyst to achieve an 82% yield of product 5. The reac-
tion did not proceed cleanly with unactivated
aromatics. As well as acetic anhydride, acetyl chloride
and isopropenyl acetate 7 performed as satisfactory
acyl donors affording the product 2 in 87 and 76%
(using 2.5 mol% of In(OTf)3) yield, respectively. The
use of alternative acyl sources such as 7 is advanta-
geous as after acylation, the resultant enolate rapidly
tautomerises to furnish acetone as the predominant
side-product.12
In summary, this paper highlights the important
results obtained in the development of an efficient yet
mild indium-catalysed acylation reaction. The scope of
the reactions outlined above are currently being
explored along with a more detailed investigation into
the structure and operation of indium catalysts.
Acknowledgements
The authors would like to thank the University of Bath
and Zeneca Agrochemicals (CASE to J.P.H.) for fund-
ing. C.G.F. would like to thank AstraZeneca for addi-
tional funding through the strategic research fund
(SRF).
This methodology has also been extended to the cata-
lytic acylation of alcohols under the optimised condi-

C. J. Chapman et al. / Tetrahedron Letters 42 (2001) 773–775
775
Scheme 4.
References
8. Sobhana Babu, B.; Balasubramanian, K. K. Tetrahedron
Lett. 2000, 41, 113–116.
1. Olah, G. A. Friedel–Crafts and Related Reactions; Inter-
science: New York, 1964.
2. Kawada, A.; Mitamura, S.; Kobayashi, S. Chem. Com-
9. (a) Ali, T.; Chauhan, K. K.; Frost, C. G. Tetrahedron
Lett. 1999, 40, 5621–5624; (b) Chauhan, K. K.; Frost, C.
G.; Love, I.; Waite, D. Synlett 1999, 1743–1744.
10. Mukaiyama, T.; Ohno, T.; Nishimura, T.; Suda, S.;
Kobayashi, S. Chem Lett. 1991, 1059–1062.
11. (a) Mukaiyama, T.; Suzuki, K.; Han, S. K.; Kobayashi,
S. Chem Lett. 1992, 435–438; (b) Kawada, A.; Mitamura,
S.; Kobayashi, S. Chem. Commun. 1996, 183–184.
12. Ishii, Y.; Takeno, M.; Kawasaki, Y.; Muromachi, A.;
Nishiyama, Y.; Sakaguchi, S. J. Org. Chem. 1996, 61,
3088–3092.
mun. 1993, 1157–1158.
3. (a) Mikami, K.; Kotera, O.; Motoyama, Y.; Sakaguchi,
H.; Maruta, M. Synlett 1996, 171–172; (b) Nie, J.; Xu, J.;
Zhou, G. J. Chem. Res. (S) 1999, 446–447.
4. Nishikido, J.; Yamamoto, F.; Nakajima, H.; Mikami, Y.;
Matsumoto, Y.; Mikami, K. Synlett 1999, 1990–1992.
5. Loh, T. P.; Pei, J.; Lin, M. Chem. Commun. 1996, 2315–
2316.
6. Loh, T. P.; Wei, L.-L. Synlett 1998, 975–976.
7. Mukaiyama, T.; Ohno, J. S.; Han, J. S.; Kobayashi, S.
Chem. Lett. 1991, 949–950.
13. (a) Ishihara, K.; Karumi, Y.; Kubota, M.; Yamamoto,
H. Synlett 1996, 839–841; (b) Fukuzawa, S.; Tsuchimoto,
T.; Hotaka, T.; Hiyama, T. Synlett 1995, 1077–1078.
.