2
56
LETTERS
SYNLETT
progressed very slowly. Comparable catalytic activity was achieved for
2.
Reviews: Kobayashi, S. Synlett 1994, 689; Kobayashi, S. J. Synth.
Org. Chem. Jpn. 1995, 53, 370.
Yb(OTf) (Table 1, entry 5). In other cases, a concomitant elimination
3
reaction forming cyclohexene was also observed as a major side-
reaction. In the control experiment using cyclohexyl bromide in place of
the corresponding mesylate, the starting materials were completely
recovered (Table 1, entry 10).
3
.
Kotsuki, H.; Ohishi, T.; Kai, K.; Tatsukawa, A. Unpublished
results. See also: Kotsuki, H.; Shimanouchi, T.; Teraguchi, M.;
Kataoka, M.; Tatsukawa, A.; Nishizawa, H. Chem. Lett. 1994,
2
159.
4
.
.
Kronenthal, D. R.; Mueller, R. H.; Kuester, P. L.; Kissick, T. P.;
Johnson, E. J. Tetrahedron Lett. 1990, 31, 1241.
The general utility of this procedure in other systems is demonstrated in
Table 2. In most cases, a large excess of aromatic compound was used
as a solvent. In the case of aromatic compounds with high boiling
points, such as naphthalene, bromobenzene, and anisole, the reactions
were conducted in refluxing carbon tetrachloride using 1.5 equiv of the
substrate (Table 2, entries 4-6). Thus, the desired reactions proceeded
with good yields in each case. The slightly decreased yield with anisole
might be ascribed to deactivation of the catalyst through complexation
5
For related examples: Matsui, M.; Yamamoto, H. Bull. Chem.
Soc. Jpn. 1995, 68, 2663. Matsui, M.; Karibe, N.; Hayashi, K.;
Yamamoto, H. Bull. Chem. Soc. Jpn. 1995, 68, 3569. Tsuchimoto,
T.; Hiyama, T.; Fukuzawa, S. Chem. Commun. 1996, 2345.
Tsuchimoto, T.; Tobita, K.; Hiyama, T.; Fukuzawa, S. Synlett
1
996, 557. Fukuzawa, S.; Tsuchimoto, T.; Hiyama, T. J. Org.
Chem. 1997, 62, 151. Tsuchimoto, T.; Tobita, K.; Hiyama, T.;
Fukuzawa, S. J. Org. Chem. 1997, 62, 6997.
9
with a methoxy function. The less-reactive nature of bromobenzene in
the Friedel-Crafts reaction is a quite common phenomenon.1 The
regioselectivity observed for toluene, naphthalene, bromobenzene, and
anisole indicates that the alkylation follows a typical electrophilic
6
.
.
Sc(OTf)3 was purchased from Pacific Metals Co., Ltd.,
Hachinohe, Aomori 031, Japan (FAX: +81-178-22-7350) and
used without further purification.
1
, 5
substitution mechanism (Table 2, entries 1 and 4-6).
The use of 2-
7
Typical experimental procedure for the synthesis of
cyclohexylbenzene: A mixture of cyclohexyl mesylate (2.0 mmol)
and Sc(OTf)3 (0.2 mmol, 10 mol%) in benzene (10 ml) was
heated at 80 °C for 4 h under nitrogen. Water was added to quench
the reaction and the organic layer was separated. The aqueous
layer was further extracted with ether. The combined extracts
pentyl or 3-pentyl mesylate as the substrate gave a mixture of 2-phenyl-
and 3-phenylpentane with the same isomer distribution (76 : 24), which
supports the notion of spontaneous rearrangement of an intermediate
carbocation species (Table 2, entries 10 and 11). Despite extensive
effort, alkylation with either cyclooctyl or menthyl mesylate failed
1
0
completely, implying serious steric repulsion.
The use of the
were dried (Na SO ) and concentrated in vacuo. The crude
2
4
mesylates of primary alcohols gave only the recovered starting
materials. In contrast to their well-known Friedel-Crafts reactions as
product was purified by preparative TLC to afford
cyclohexylbenzene (92%) as a colorless oil. The catalyst could be
recovered by crystallization from the aqueous phase by gradual
evaporation of water,8 and was used repeatedly without a
significant loss of activity (2nd run: 89%, 8 h; 3rd run: 83%, 12 h).
1
electrophiles, no reaction was observed for tertiary alcohols such as t-
butanol.
In conclusion, we have found an efficient method for alkylating an
aromatic compound with mesylates derived from secondary alcohols in
8
.
.
The contaminating methanesulfonic acid was removed by
decantation.
1
1
the presence of a catalytic amount of Sc(OTf)3. Even though several
methods have been reported thus far for the Friedel-Crafts alkylation of
9
In contrast, RE(OTf) -catalyzed Friedel-Crafts acylation of
3
anisoles proceeds in quite high yields. See for example: Kawada,
A.; Mitamura, S.; Kobayashi, S. Synlett 1994, 545. Kobayashi, S.;
Moriwaki, M.; Hachiya, I. Synlett 1995, 1153. Kobayashi, S.;
Moriwaki, M.; Hachiya, I. J. Chem. Soc., Chem. Commun. 1995,
1
aromatic molecules, the present method appears to be of great value
with regard to its simplicity and high efficiency. Further studies on the
application of this method to natural product synthesis are now in
progress.
1527. Kawada, A.; Mitamura, S.; Kobayashi, S. Chem. Commun.
1
996, 183. Mikami, K.; Kotera, O.; Motoyama, Y.; Sakaguchi, H.;
References and Notes
Maruta, M. Synlett 1996, 171. Kobayashi, S.; Moriwaki, M.;
Hachiya, I. Bull. Chem. Soc. Jpn. 1997, 70, 267.
1.
For reviews of Friedel-Crafts alkylation, see: Price, C. C. Org.
React., 1946, 3, 1; Olah, G. A. Friedel-Crafts and Related
Reactions, Wiley-Interscience: New York, 1964, Vol. II, part 1;
Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. In
Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I., Eds.;
Pergamon Press: Oxford, 1991, Vol. III, pp 293-339; March, J.
Advanced Organic Chemistry, 4th Ed., Wiley-Interscience: New
York, 1992, pp 534-539.
1
0. Only a complex hydrocarbon mixture was obtained.
1
1. These reactions can be also facilitated under TfOH-catalyzed
conditions, but this subject will be reported in a forthcoming
communication.