Scandium(III) Triflate-Catalyzed Friedel-Crafts Alkylation Reactions

Article abstract of DOI:10.1021/jo970599u

The Sc(OTf)₃-catalyzed Friedel-Crafts alkylation reaction with an alcohol, an arenecarbaldehyde or an arenecarbaldehyde acetal as the alkylating agent affords a diarylmethane or an allylbenzene derivative highly selectively. The salient feature of this reaction is that only a catalytic amount of Sc(OTf)₃ can effect the reaction. Furthermore, Sc(OTf)₃ is recoverable and reusable after the synthetic reaction. The Sc(OTf)₃-catalyzed benzylation using an arenecarbaldehyde and 1,3-propanediol or their acetal affords diarylmethane as a sole product in excellent yields in sharp contrast to the original Friedel-Crafts reaction. Since no reaction occurs in the absence of 1,3-propanediol, the reaction is considered to proceed through a redox process including a hydride shift. The hydride shift mechanism is strongly supported by the experimental evidence. The reaction of benzaldehyde with benzene in the presence of 1,3-propanediol-1,1,3,3,-d₄ gives rise to the deuterium incorporation into the benzylic carbon of diphenylmethane. Worthy of note is that 1,3-propanediol acts as the hydride source. Herein, diphenylmethyl 3-hydroxypropyl ether is assumed to be the most likely intermediate. In this reaction, Sc(OTf)₃ catalyst effectively promotes initial acetal formation, electrophilic aromatic substitution, and successive intramolecular hydride transfer.

Full text of DOI:10.1021/jo970599u

J . Org. Chem. 1997, 62, 6997-7005
6997
Sca n d iu m (III) Tr ifla te-Ca ta lyzed F r ied el-Cr a fts Alk yla tion
Rea ction s
Teruhisa Tsuchimoto,† Kazuo Tobita,‡ Tamejiro Hiyama,† and Shin-ichi Fukuzawa*,‡
Research Laboratory of Resources Utilization, Tokyo Institute of Technology, 4259 Nagatsuda,
Midori-ku, Yokohama 226, J apan, and Department of Applied Chemistry, Chuo University,
Kasuga, Bunkyo-ku, Tokyo 112, J apan
Received April 2, 1997X
The Sc(OTf)3-catalyzed Friedel-Crafts alkylation reaction with an alcohol, an arenecarbaldehyde
or an arenecarbaldehyde acetal as the alkylating agent affords a diarylmethane or an allylbenzene
derivative highly selectively. The salient feature of this reaction is that only a catalytic amount of
Sc(OTf)3 can effect the reaction. Furthermore, Sc(OTf)3 is recoverable and reusable after the
synthetic reaction. The Sc(OTf)3-catalyzed benzylation using an arenecarbaldehyde and 1,3-
propanediol or their acetal affords diarylmethane as a sole product in excellent yields in sharp
contrast to the original Friedel-Crafts reaction. Since no reaction occurs in the absence of 1,3-
propanediol, the reaction is considered to proceed through a redox process including a hydride
shift. The hydride shift mechanism is strongly supported by the experimental evidence. The
reaction of benzaldehyde with benzene in the presence of 1,3-propanediol-1,1,3,3,-d4 gives rise to
the deuterium incorporation into the benzylic carbon of diphenylmethane. Worthy of note is that
1,3-propanediol acts as the hydride source. Herein, diphenylmethyl 3-hydroxypropyl ether is
assumed to be the most likely intermediate. In this reaction, Sc(OTf)3 catalyst effectively promotes
initial acetal formation, electrophilic aromatic substitution, and successive intramolecular hydride
transfer.
In tr od u ction
these, RE(III) trifluoromethanesulfonates [RE(OTf)3] are
assumed to be the strongest due to the least nucleophilic
triflate counteranion. In contrast to most of the metal
triflates that are usually prepared under strictly anhy-
drous conditions, RE(OTf)3 are generally prepared in
aqueous solution.5 It has been recently demonstrated
that RE(OTf)3 are particularly useful and unique in car-
bon-carbon bond forming reactions in aqueous media.6-9
Therefore, RE(OTf)3 have advantages over such conven-
tional Lewis acids as TiCl4, AlCl3, SnCl4, and BF3‚OEt2.
We disclose here in detail the Sc(OTf)3-catalyzed Friedel-
Crafts benzylation and allylation reactions of various
aromatic compounds using the corresponding alcohols,
aldehydes, and acetals as alkylating agents.10
The alkylation of an aromatic ring through the Friedel-
Crafts reaction is of great synthetic significance in view
of laboratory synthesis and particularly industrial
production.1-4 For example, industrial processes for
high-octane gasoline, ethylbenzene, synthetic rubber,
plastics, and detergent alkylates are based on this
reaction. Although such a wide variety of alkylating
agents have been used such as alkyl halides, alkenes,
alcohols, ethers, and aldehydes, the standard conditions
for the Friedel-Crafts alkylation employ an alkyl halide
and a Lewis acid catalyst such as aluminum(III) chloride.
The conditions, however, coproduce a hydrogen halide
which often induces side reactions and induces the
production of many byproducts. In addition, disposal of
the aluminum hydroxide residue excreted by usual
workup causes additional environmental problems. There-
fore, a reaction process which does not generate the
hydrogen halide byproducts has been the target of
extensive research. Furthermore, it has been desirable
to use a Lewis acid catalyst resistant to aqueous media.
Resu lts a n d Discu ssion
Sc(OTf)3-Ca ta lyzed Fr iedel-Cr a fts Alk yla tion Re-
a ction w ith Ben zyl Alcoh ols. Alcohols are preferable
alkylating agents rather than alkyl halides because
hydrogen halides are not coproduced. However, the
reaction with alcohols requires considerable amounts of
AlCl3, since the alcohols and/or in situ generated water
deactivates the catalyst. Therefore, we paid attention
to the characteristics and reactivities of RE(III) com-
Because of such salient features as their hard character
and their specific coordination numbers, rare earth(III)
(RE) salts are expected to be strong Lewis acids. Among
* Author to whom correspondence should be addressed. Phone:
+81-3-3817-1916. Fax: +81-3-3817-1895. E-mail: fukuzawa@apchem.
chem.chuo-u.ac.jp.
(5) (a) Forsberg, J . H.; Spaziano, V. T.; Balasubramanian, T. M.;
Liu, G. K.; Kinsley, S. A.; Duckworth, C. A.; Poteruca, J . J .; Brown, P.
S.; Miller, J . L. J . Org. Chem. 1987, 52, 1017. (b) Collins, S.; Hong, Y.
Tetrahedron Lett. 1987, 28, 4391. (c) Almasio, M.-C.; Arnaud-Neu, F.;
Schwing-Weill, M.-J . Helv. Chim. Acta 1983, 66, 1296.
† Tokyo Institute of Technology.
‡ Chuo University.
X Abstract published in Advance ACS Abstracts, September 15, 1997.
(1) Olah, G. A. Friedel-Crafts and Related Reactions;
Wiley-Interscience: New York, 1964; Vol. II, Part 1.
(2) Roberts, R. M.; Khalaf, A. A. Friedel-Crafts Alkylation Chem-
istry. A Century of Discovery, Dekker: New York, 1984.
(3) Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. Friedel-Crafts
Alkylations in Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, 1991.
(6) (a) Kobayashi, S. Chem. Lett. 1991, 2187. (b) Kobayashi, S.;
Hachiya, I. Tetrahedron Lett. 1992, 33, 1625. (c) Hachiya, I.; Koba-
yashi, S. J . Org. Chem. 1993, 58, 6958. (d) Kobayashi, S.; Ishitani, H.
J . Chem. Soc., Chem. Commun. 1995, 1379. (e) Mikami, K.; Kotera,
O.; Motoyama, Y.; Sakaguchi, H. Synlett 1995, 975. (f) Fujiwara, K.;
Tokiwano, T.; Murai, A. Tetrahedron Lett. 1995, 36, 8063. (g) Depu,
C.; Libing, Y.; Peng, G. W. Tetrahedron Lett. 1996, 37, 4467. (h)
Kotsuki, H.; Teraguchi, M.; Shimomoto, N.; Ochi, M. Tetrahedron Lett.
1996, 37, 3727.
(4) For
a pharmacologically important intramolecular Friedel-
Crafts benzylation reaction, see; Yamamoto, T.; Fukumoto, M.; Sakaue,
(7) For reviews, see: (a) Kobayashi, S. Synlett 1994, 689. (b)
Marshman, R. W. Aldrichimica Acta 1995, 28, 77.
N.; Furusawa, T.; Tashiro, M. Synthesis 1991, 699.
S0022-3263(97)00599-9 CCC: $14.00 © 1997 American Chemical Society

6998 J . Org. Chem., Vol. 62, No. 20, 1997
Tsuchimoto et al.
Ta ble 1. REX3-Ca ta lyzed F r ied el-Cr a fts Ben zyla tion
Ta ble 2. Sc(OTf)3-Ca ta lyzed Ben zyla tion Rea ction of
Ar om a tic Com p ou n d s w ith Ben zyl Alcoh ola
w ith Ben zyl Alcoh ola
run
REX3
YbCl3
aromatics
product
yield (%)b
aromatic time
yield
(%)b
ratio of
o:m:p
run alcohol
compd
(h)
product
1
2
3
4
5
6
7
8
9
10
11
12
13
PhH (2a )
3a
trace
trace
quant
quant
24
ScCl3
1
2
1a
2a
2b
2c
2d
2d
2e
2e
2f
6
4
4
1
1.5
1
1
3a
3b
3c
3d
3d
3e
3e
3f
91
Nd(OTf)3
Sm(OTf)3
Yb(OTf)3
Sc(OTf)3
Y(OTf)3
Nd(OTf)3
Sm(OTf)3
Sc(OTf)3
Nd(OTf)3
Sm(OTf)3
Sc(OTf)3
quant
quant
90c
48:7:45
3
4
5
6
7
8
9
91
quant
trace
87c
57:trace:43
PhMe (2b)
3b
3c
5c
quantd 59:1:40
94c
4
79c,e
91d,e
91
quantc
trace
75
2f
4
3f
p-xylene (2c)
10
11
12
13
14
15
1b
2a
2c
2c
2a
2c
2a
3
2
2.5
3
1
3g
3h
3h
3i
3j
3k
73
quant
quantd
93
1c
1d
a
Reaction conditions: 1a (1.0 mmol), aromatic compound 2 (5.0
quant
75
b
mL), and RE(III) compound (0.1 mmol), 115-120 °C. GLC yield.
8
c Isomer ratio was o:m:p ) 48:7:45.
a
Reaction conditions: benzyl alcohol (1.0 mmol), an aromatic
b
compound (5.0 mL), and Sc(OTf)3 (0.1 mmol), 115-125 °C. GLC
yield. c The reaction was carried out with 5.0 molar equiv of the
aromatic substrate in 1,2-dichloroethane (5.0 mL) at the reflux
pounds and studied the RE(III)-catalyzed Friedel-Crafts
reaction of benzene (2a ), toluene (2b), or p-xylene (2c)
with benzyl alcohol (1a ) as the alkylating agents (eq 1).
The results are summarized in Table 1.
d
temperature. The reaction was carried out with 5.0 molar equiv
of the aromatic substrate in nitromethane (5.0 mL) at the reflux
temperature. e Isomer ratio was approximately 1:1.
that RECl3 could repeatedly be used for the benzylation
of aromatic substrates with a benzylic halide.11 We first
studied the reaction of 2a with 1a using ScCl3 and YbCl3
and obtained only a trace amount of diphenylmethane
(3a ), probably due to the weak Lewis acidity of the
catalyst (runs 1 and 2). We then used RE(OTf)3 for the
reaction of 2a with 1a and found Nd(OTf)3, Sm(OTf)3,
and Sc(OTf)3 efficiently gave 3a (runs 3, 4 and 6),
whereas the yield of 3a was lower with Yb(OTf)3 or
Y(OTf)3 (runs 3-7). For the reaction of toluene (2b) or
p-xylene (2c) with 1a , Sc(OTf)3 exhibited the highest
activity and afforded (methylphenyl)phenylmethane (3b)
or (dimethylphenyl)phenylmethane (3c) in quantitative
yields, respectively, without any contamination of byprod-
ucts (runs 10 and 13). Olah et al. prepared triflates of
boron, aluminum, and gallium12 and applied them to the
Friedel-Crafts alkylation using alkyl halides to observe
that 50 mol % of the catalyst under strictly anhydrous
conditions were necessary because these triflates were
extremely moisture sensitive. In contrast, RE(OTf)3 is
stable to moisture and easy to be handled. Thus, the
RE(OTf)3-catalyzed Friedel-Crafts reaction with benzyl
alcohol could be carried out in an aromatic solvent simply
distilled without any care. These results prompted us
to survey the scope of the Sc(OTf)3-catalyzed benzylation
reaction using various benzylic alcohols and aromatic
solvents. The results are summarized in Table 2.
Although the recycle of the Friedel-Crafts catalysts
is believed to be impractical, Fujiwara et al. demonstrated
(8) For selected references on some organic reactions using lan-
thanide(III) triflate, see: (a) Kobayashi, S.; Hachiya, I.; Takahori, T.;
Araki, M.; Ishitani, H. Tetrahedron Lett. 1992, 33, 6815. (b) Inanaga,
J .; Yokoyama, Y.; Hanamoto, T. Tetrahedron Lett. 1993, 34, 2791. (c)
Kobayashi, S.; Hachiya, H.; Ishitani, H.; Araki, M. Tetrahedron Lett.
1993, 34, 4535. (d) Fukuzawa, S.; Tsuchimoto, T.; Kanai, T. Bull.
Chem. Soc. J pn. 1994, 67, 2227. (e) Kobayashi, S.; Ishitani, H. J . Am.
Chem. Soc. 1994, 116, 4083. (f) Meguro, M; Asao, N.; Yamamoto, Y.
J . Chem. Soc., Perkin Trans. 1 1994, 2597. (g) Meguro, M.; Asao, N.;
Yamamoto, Y. J . Chem. Soc., Chem. Commun. 1995, 1021. (h)
Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S.; Hachiya, I.
Synlett 1995, 233. (i) Kobayashi, S.; Moriwaki, M.; Hachiya, I. Synlett
1995, 1153. (j) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis
1995, 1195. (k) Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto,
H. J . Am. Chem. Soc. 1995, 117, 4413. (l) Kobayashi, S.; Ishitani, H.;
Nagayama, S. Chem. Lett. 1995, 423. (m) Kobayashi, S.; Araki, M.;
Yasuda, M. Tetrahedron Lett. 1995, 36, 5773. (n) Ishihara, K.; Karumi,
Y.; Kubota, M.; Yamamoto, H. Synlett 1996, 839. (o) Hanamoto, T.;
Sugimoto, Y.; Yokoyama, Y.; Inanaga, J . J . Org. Chem. 1996, 61, 4491.
(p) Kobayashi, S.; Ishitani, H.; Komiyama, S.; Oniciu, D. C.; Katritzky,
A. R. Tetrahedron Lett. 1996, 37, 3731. (q) El Gihani, M. T.; Heaney,
H.; Shuhaibar, K. F. Synlett, 1996, 871.
The reaction of a substituted benzyl alcohol 1a , 1b, 1c,
or 1d with benzene (2a ) proceeded smoothly to afford the
corresponding diarylmethane 3a , 3g, 3i, or 3k in high
yield (runs 1, 10, 13, or 15).13 In every case, the reaction
was performed using arene in excess. Toluene (2b),
p-xylene (2c), or mesitylene (2d ) also reacted satisfac-
(10) Preliminary reports on the Friedel-Crafts alkylation reaction
using Sc(OTf)3 as the catalyst: (a) Tsuchimoto, T.; Tobita, K.; Hiyama,
T.; Fukuzawa, S. Synlett 1996, 557. (b) Tsuchimoto, T.; Hiyama, T.;
Fukuzawa, S. Chem. Commun. 1996, 2345.
(11) Mine, N.; Fujiwara, Y.; Taniguchi, H. Chem Lett. 1986, 357.
(12) Olah, G. A.; Farooq, O.; Farnia, S. M. F.; Olah, J . A. J . Am.
Chem. Soc. 1988, 110, 2560.
(13) The acylation reaction of benzene or toluene with acid chlorides
or anhydrides using RE(OTf)3 as a catalyst scarcely takes place. (a)
Kawada, A.; Mitamura, S.; Kobayashi, S. J . Chem. Soc., Chem.
Commun. 1993, 1157; 1996, 183; Synlett 1994, 545. (b) Kobayashi,
S.; Moriwaki, M.; Hachiya, I. Bull Chem. Soc. J pn. 1997, 70, 267.
(9) Sc(OTf)3 is also applicable to the combinatorial synthesis; see:
Kobayashi, S.; Moriwaki, M.; Akiyama, R.; Suzuki, S.; Hachiya, I.
Tetrahedron Lett. 1996, 37, 7783.

Scandium(III) Triflate-Catalyzed Alkylation Reactions
J . Org. Chem., Vol. 62, No. 20, 1997 6999
Ta ble 3. F r ied el-Cr a fts Allyla tion Rea ction of Ben zen e
torily with 1a (runs 2-5, 11, 12, and 14). For the
reaction of high boiling point aromatics like 2d , anisole
(2e), and 1,2-dimethoxybenzene (2f), the reaction was
conveniently carried out with 5 molar equiv of the
substrate relative to 1a in 1,2-dichloroethane or in
nitromethane as the solvent (runs 4-9). It is noteworthy
that the reaction in nitromethane proceeded quantita-
tively (runs 5, 7, 9, and 12). The reaction in dichlo-
romethane or carbon disulfide at the reflux temperature
gave only a trace amount of the benzylation product. An
electron-donating group on aromatic substrates some-
what enhanced the benzylation reaction. The isomer
distributions starting with substituted arenes were ortho-
para preference in accord with the typical electrophilic
aromatic substitution (runs 2, 6, and 7). These observa-
tions are consistent with those obtained with AlCl3-
CH3NO2 or TiCl4 catalyst.14 By contrast, neither of
4-nitro-, 4-methoxy-, or 4-hydroxy(phenylmethanol) un-
derwent the reaction under the similar conditions. These
functional groups might have formed complexes with
Sc(OTf)3 to interrupt the reaction. Formation of dibenzyl
ether (4), dehydration products of 1, was observed at the
early stage of the reaction but was negligible at the end
of the reaction.15 Indeed, 4 was shown to react with 2a
or 2c to furnish 3a or 3c in 39% or 43% yield, respec-
tively, under the same reaction conditions (eq 2).
w ith Allyl Alcoh ola
a
Reaction conditions: 5 (1.0 mmol), 2a (5.0 mL), and Sc(OTf)3
b
(0.1 mmol), 115-120 °C.
determined by GLC. 6c was isolated in 81% yield after chro-
GLC yield. c Isomer ratios were
d
matography.
the allylated products are generally low. The protocol is
also applicable to the allylation reactions of aromatic
compounds with allylic alcohols 5 as the alkylating
agents.
As outlined in Table 3, the Friedel-Crafts allylation
reaction of 2 with allylic alcohol 5 using Sc(OTf)3 as a
catalyst proceeded successfully to afford the correspond-
ing allylbenzene derivatives 6 in good to excellent yields
without any troublesome side reactions (eq 3), However,
In some cases dibenzylated products were formed by
the subsequent reaction of the benzylation products in
small amount. With 1-phenylethanol as the alkylating
agent, styrene was detected as a major product along
with several unidentified products. The reaction of
benzene with benzhydrol afforded triphenylmethane in
66% yield.
The present method is also applicable to the prepara-
tive-scale synthesis using benzyl alcohol (20 mmol),
benzene (100 mL), and Sc(OTf)3 (2.0 mmol) at 115 °C for
8 h. 3a was isolated in 81% yield after distillation at 97
°C/3.0 mmHg.
Sc(OTf)3-Ca ta lyzed Fr ied el-Cr a fts Alk yla tion Re-
a ction w ith Allylic Alcoh ols. Vanillin, a vivid fra-
grance material isolated from vanilla fruits in the orchid
family, is prepared from eugenol in an industrial process.
Eugenol, in turn, is prepared by allylation of guaiacol.
Thus, the Friedel-Crafts allylation reaction of aromatic
compounds is straightforward tool for the synthesis of
allylbenzene derivatives. It is well-known that a metal
halide Lewis acid catalyst such as AlCl3 exclusively
induces the allylic substitution by aromatics.2 However,
HCl generated by the reaction of AlCl3 and an allylic
alcohol or H2O brings about various side reactions as well
as the addition to the double bond. Thus, the yields of
the reaction of benzene with 2-cyclohexen-1-ol did not
produce the allylation product under the reaction condi-
tions. As expected, the reactions occurred always at the
less-substituted allylic carbon. Worthy of note is that no
rearrangement of the position of the double bond took
place under the reaction conditions. It should be noted
that the reaction of 1-penten-3-ol (5b) or 2-penten-1-ol
(5c) with benzene led to the same product 6b with a
slightly different product ratio (runs 2 and 3). These
results suggest that the same alkylation products are
produced irrespective of the starting regioisomeric allylic
alcohols. Similarly, both cis- and trans-2-hexenol (5d and
5e) with benzene preferentially gave the trans-2-hex-
enylbenzene (6c) in excellent yields, although the trans/
cis ratio was slightly dependent on the structure of the
starting allyl alcohol (runs 4 and 5). The stereochemistry
of 6 derived from monosubstituted allylic alcohols and
2a was proved to be time-independent. Thus, the reac-
tion should proceed under kinetic control. Namely, no
equilibrium between the cis and trans isomers is taking
place under the reaction conditions.
(14) The isomer distributions of 3 were determined by 13C NMR
spectra or GC analysis by comparing with those of the authentic
samples which were prepared by the reaction of the aromatics with
the corresponding benzyl halides using TiCl4 or AlCl3-MeNO3. (a)
Olah, G. A.; Kobayashi, S.; Tashiro, M. J . Am. Chem. Soc. 1972, 94,
7448. (b) Olah, G. A.; Olah, J . A. J . Am. Chem. Soc. 1984, 106, 5248.
(15) Solid superacid-catalyzed benzylation reaction induces the
formation of the dehydration products as a byproduct. Yamamoto, T.;
Hideshima, C.; Prakash, G. K. S.; Olah, G. A. J . Org. Chem. 1991, 56,
2089.
Recover y a n d Reu se of Sc(OTf)3. Evaporation of
the aqueous layer of the reaction mixture allowed Sc(OTf)3
to be recovered as a white powder, which was further
dried by heating in vacuo at 180 °C and was employed
for the same reaction. 3a was obtained in 89% yield in
the second run, 84% yield in the third run.

7000 J . Org. Chem., Vol. 62, No. 20, 1997
Tsuchimoto et al.
been investigated independently by Shudo18 and Olah,19
and the product distribution proved to be dependent on
the reaction conditions: triphenylmethane was exclu-
sively produced at ambient temperature when a large
excess amount of TfOH (100 equiv to benzaldehyde) was
used as the acid catalyst. However, this type of the
Friedel-Crafts reaction has eluded synthetic interest due
to the inevitable use of a large excess amount of TfOH
and formation of a complex mixture of the products.
Recently, gallium dichloride was reported to promote the
reductive Friedel-Crafts reaction of both aliphatic and
aromatic carbonyl compounds, but here again the use of
gallium dichloride in excess was essential.20 Thus, the
catalytic and practical Friedel-Crafts-type alkylation
reaction using arenecarbaldehydes 7 has remained yet
to be explored.21
Ta ble 4. Sc(OTf)3-Ca ta lyzed F r ied el-Cr a fts Ben zyla tion
Rea ction of Ben zen e w ith Ben za ld eh yd e in th e P r esen ce
of Va r iou s Alcoh olsa
During the course of our investigation of the Friedel-
Crafts alkylation reaction using Sc(OTf)3,9a we found that
arenecarbaldehyde 7, upon treatment with 1,3-pro-
panediol (8c) and a catalytic quantity of Sc(OTf)3, cleanly
underwent an unprecedented reductive Friedel-Crafts
benzylation with an aromatic compound (eq 4).9b Details
a
The reaction was carried out with benzaldehyde (1.0 mmol),
b
diol (1.1 mmol), benzene (5.0 mL), and Sc(OTf)3 (0.1 mmol). GLC
yield. c The corresponding acetals were obtained: run 1 (54%
d
yield), run 2 (72% yield), run 3 (94% yield). Complex mixture.
e 2.2 molar equiv of alcohol to benzaldehyde were used.
are discussed herein of the Sc(OTf)3-catalyzed reductive
Friedel-Crafts reaction using an arenecarbaldehyde 7
as the electrophile. We also refer to the mechanism of
the reaction.
To begin with, we examined the efficacy of an alcohol
in the reaction of 2a with benzaldehyde (7a ) in the
presence of Sc(OTf)3 as a catalyst. The results are
summarized in Table 4. When a solution of 7a (1.0 mmol)
and 8c (1.1 mmol) in 2a (5.0 mL) was heated to reflux
for 10 h in the presence of a catalytic amount of Sc(OTf)3,
diphenylmethane (3a ) was obtained in good yields. It is
worth noting that the benzylation reaction took place by
a redox process, and none of triphenylmethane, triphen-
Similar recovery and reuse of RE(OTf)3 catalyst is
reported by Kobayashi et al. who demonstrated that
RE(OTf)3 recovered from the aqueous layer after the
Friedel-Crafts reaction could be reused for the same
reaction.5,6 That Sc(OTf)3 is reusable is the striking
feature; nevertheless scandium is uncommon and expen-
sive. Thus, the Sc(OTf)3-catalyzed organic reactions
should find wide applications in industrial processes.
Sc(OTf)3-Ca ta lyzed Fr ied el-Cr a fts Alk yla tion Re-
a ction w ith Ar en eca r ba ld eh yd es in th e P r esen ce
of 1,3-P r op a n ed iol. Less attention has been focused
on the acid-catalyzed condensation reaction of aromatic
compounds 2 with arenecarbaldehydes 7 because of the
formation of many products such as triarylmethane,
triarylmethanol, diarylmethane, and anthracene deriva-
tives,16 although the prototype has been recognized since
1886.17 Recently, the mechanism of this reaction has
(18) Saito, S.; Ohwada, T.; Shudo, K. J . Am. Chem. Soc. 1995, 117,
11081.
(19) Olah, G. A.; Rasul, G.; York, C.; Prakash, G. K. S. J . Am. Chem.
Soc. 1995, 117, 11211 and references cited therein.
(20) (a) Hashimoto, Y.; Hirata, K.; Kihara, N.; Hasegawa, M.; Saigo,
K. Tetrahedron Lett. 1992, 33, 6351. (b) Hashimoto, Y.; Hirata, K.;
Kagoshima, H.; Kihara, N.; Hasegawa, M.; Saigo, K. Tetrahedron 1993,
49, 5969.
(16) Roberts, R. M.; EI-Khawaga, A. M.; Sweeney, K. M.; EI-Zohry,
M. F. J . Org. Chem. 1987, 52, 1959 and references cited therein.
(17) Griepentrog, H. Ber. Dtsch. Chem. Ges. 1886, 19, 1876.
(21) Climent, M. J .; Corma, A.; Garce´ıa, H.; Primo, J . J . Catal. 1991,
130, 138.

Scandium(III) Triflate-Catalyzed Alkylation Reactions
J . Org. Chem., Vol. 62, No. 20, 1997 7001
Ta ble 5. Effect of Lew is Acid Ca ta lyst for th e
Ta ble 6. Sc(OTf)3-Ca ta lyzed Red u ctive F r ied el-Cr a fts
Rea ction of Ar en es w ith Ar en eca r ba ld eh yd e a n d
1,3-P r op a n ed iola
F r ied el-Cr a fts Ben zyla tion Rea ction a
Lewis
acid
yield (%)
Lewis
acid
yield (%)
run
of 3bb
run
of 3bb
aromatic time
yield
(%)b
ratio of
o:m:p
run aldehyde
compd
(h) product
1
2
3
4
5
6
7
ZnCl2
AlCl3
SnCl4
SnCl4
TiCl4
0
2
97
2c
0
8
9
Sc(OTf)3
Sc(OTf)3
Nd(OTf)3
Y(OTf)3
Sm(OTf)3
Yb(OTf)3
TfOH
98
70c
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
7a
2a
2b
2c
2e
2e
2e
2a
2b
2c
2a
2b
2a
2b
2c
2a
2b
2b
2a
10
10
10
10
10
10
8.5
6
8
10
16
17.5
16
17
20
16
10
6
3a
3b
3c
3e
3e
3e
3g
3l
3h
3m
3n
3i
70
97
96
10
11
12
13
14
42:7:51
0
0
0
36c
37d
nre
64
49:trace:51
45:trace:55
BF3‚OEt2
ScCl3
0
0
96
7b
a
The reaction was carried out with 7a (1.0 mmol), Lewis acid
quant 34:4:62
73
trace
30
91
89
quant
75
quant 34:5:61
68 25:5:75
b
(0.1 mmol), and 2b (5.0 mL) at reflux temperature. GLC yield.
c 2a instead of 2b was used.
7c
7d
37:3:60
41:9:50
ylmethanol, or anthracene was produced, in sharp con-
trast to the original Friedel-Crafts reactions. As sum-
marized in Table 4, the yield of 3a depended greatly upon
the structure of the alcohol. The benzylation reaction did
not take place at room temperature or at reflux conditions
when a 1,2-diol such as 2,3-butanediol (8a ) or 1,2-
ethanediol (8b) was used; the corresponding 1,3-dioxo-
lanes were formed in moderate to high yields (runs 1-3).
The benzylation reaction of 2a using 8c in the presence
of Sc(OTf)3 at reflux temperature gave 3a in 70% yield
without any troublesome side reactions (run 4). Worthy
of note is that the reaction with the same reagent system
at ambient temperatures furnished 2-phenyl-1,3-dioxane
in 93% yield instead of 3a .22 Accordingly, the reaction
pathway to an acetal or a diarylmethane can be readily
controlled by an appropriate choice of the reaction
temperature with the same substrates. With 2-ethly-1,3-
propanediol (8e), 3a was again obtained in 68% yield (run
6), but with a low yield of the products formed in the
reaction with 2,4-pentanediol (8d ) or 1,4-butanediol (8g)
(runs 5 and 8). The reaction with 2,4-dimethyl-2,4-
pentanediol (8f) resulted in a complex mixture of products
(run 7). With methanol (8h ), 2-propanol (8i), or 1-butanol
(8j), no product or only a small amount of the product
formed, with 7a being recovered (runs 9-11). After
screening various alcohols, we concluded that 8c was the
coreagent of choice to accomplish the Friedel-Crafts
benzylation reaction. In the absence of 8c, no reaction
took place. Thus, the use of 8c in this reaction is
essential.
The catalytic activity of several Lewis acid catalysts
for the Friedel-Crafts reaction of toluene (2b) with 7a
in the presence of 8c was examined. The results are
summarized in Table 5. All reactions were carried out
at reflux temperature of 2b. Conventional Lewis acids
like ZnCl2, AlCl3, TiCl4, and BF3‚OEt2 were totally
inactive except for SnCl4 (runs 1-3, 5, and 6). Although
SnCl4 effectively catalyzed benzylation of 2b with 7a , the
reaction of 2a with 7a using SnCl4 as the catalyst
resulted in the formation of a trace amount of 3a (run
4). The reaction was next performed using rare earth(III)
compounds as the catalyst. Sc(OTf)3 was found to be a
quite efficient catalyst for the reaction of 2b with 7a to
afford (methylphenyl)phenylmethane (3b) in a quantita-
tive yield (run 8), whereas other rare earth(III) com-
pounds exhibited no catalytic activity. Sc(OTf)3 was also
effective for the reaction of 2a with 7a (run 9). Brønsted
acid like TfOH also catalyzed the Friedel-Crafts reaction
effectively (run 14); the details of the results are already
reported.23 On the basis of these results, we concluded
3o
3j
7e
7f
7g
7h
3p
3q
3r
f
-
a
The reaction was carried out with 7 (1.0 mmol), 1,3-pro-
panediol (1.1 mmol), 2 (5.0 mL), and Sc(OTf)3 (0.1 mmol) at 125
b
°C. GLC yield. c The reaction was carried out with 5.0 molar
equiv of anisole in nitromethane (5.0 mL) at the reflux tempera-
d
ture. The reaction was carried out with 5.0 molar equiv of anisole
in 1,2-dichloroethane (5.0 mL) at the reflux temperature. e The
reaction was carried out with 5.0 molar equiv of anisole in
chloroform (5.0 mL) at the reflux temperature. f Complex mixture.
that Sc(OTf)3 was the promising catalyst to achieve the
Friedel-Crafts reaction of aromatics with arenecarbal-
dehydes.
These results prompted us to survey the scope of the
reaction. The results are summarized in Table 6. Aro-
matic compounds except anisole (2e) were utilized not
only as the substrate but also as the reaction medium.
With 7a as the benzylation reagent, the Friedel-Crafts
products were produced in yields ranging from 37 to 97%
(runs 1-3 and 5). The yields of the alkylation products
were generally improved by use of 2b or 2c. However,
the reaction of 2e resulted in lower yields of the desired
product due probably to side reactions, although the
starting substrate was completely consumed. The side
reactions were suppressed to some extent by the use of
1,2-dichloroethane or nitromethane as the solvent (runs
4 and 5). The reaction of 2e in chloroform resulted in no
reaction due to its lower boiling point (run 6). When the
protocol was applied to the reaction of aldehyde 7b, 7c,
7d , 7e, or 7f, bearing an electron-donating or -withdraw-
ing group at para position, high to quantitative yields of
the corresponding diarylmethane were obtained with 2a ,
2b, or 2c. Similarly, 1-naphthyl aldehyde (7g) reacted
with 2b to afford a regioisomeric mixture of 1-naphth-
ylmethylated toluenes (3r ) in 68% yield (run 17). How-
ever, treating pyridine-2-carbaldehyde with 2a under the
reaction condition afforded the corresponding 1,3-dioxane
derivative in a high yield instead of the diarylmethane.
Presumably, nitrogen within the pyridine ring might
have brought about the complexation with Sc(OTf)3 to
prevent further activation of the acetal ring. The posi-
tional selectivity of the benzylation of substituted arenes
was the ortho-para preference in conformity with that
observed in the usual Lewis acid-catalyzed Friedel-
Crafts reaction using benzyl halide or benzyl alcohol.14
The reaction rate significantly increased with the stron-
(22) Fukuzawa, S.; Tsuchimoto, T.; Hotaka, T.; Hiyama, T. Synlett
1995, 1077.
(23) Fukuzawa, S.; Tsuchimoto, T.; Hiyama, T. J . Org. Chem. 1997,
62, 151.

7002 J . Org. Chem., Vol. 62, No. 20, 1997
Tsuchimoto et al.
Ta ble 7. Sc(OTf)3-Ca ta lyzed Red u ctive F r ied el-Cr a fts
chemical yields of 3 were virtually the same as those
observed in the reaction starting with a mixture of 7
and 8c.
Rea ction of Ar en es w ith Ar en eca r ba ld eh yd e Aceta ls
aromatic time
yield
(%)b
ratio of
o:m:p
run aldehyde
compd
(h)
product
1
2
3
4
5
6
7
8
9
10
11
12
13
9a
2a
2b
2c
2d
2a
2b
2c
2a
2b
2c
2a
2b
2b
22
10
10
10
9
3a
3b
3c
3d
3g
3l
3h
3i
3o
3j
64
Rea ction Mech a n ism
quant 40:7:53
For the mechanism of this type of the Friedel-Crafts
benzylation, Olah and Shudo proposed that diprotonated
benzaldehyde was involved and behave as a highly
reactive electrophilic intermediate.18,19 Although Lewis
acid generally activates the carbonyl function to afford
an electrophilic species reactive to nucleophiles, com-
plexation of Sc(OTf)3 with arenecarbaldehyde appears to
give a weak electrophile rather than the diprotonated
species, and thus its reactivity toward benzene (2a )
should remain at a low level. Since no reaction took place
in the absence of 1,3-propanediol and no triarylmethane,
triarylmethanol, or anthracene was isolated, the reaction
appears to proceed through a process completely different
from the original Friedel-Crafts reactions: a possible
reaction pathway should be a redox process if one
considers the formation of diarylmethanes. Without the
redox process, the expected products must be triphenyl-
methane and/or diphenylmethyl ether. From a mecha-
nistic viewpoint, we decided to confirm the redox reaction
and to demonstrate what was the hydride source. We
finally have disclosed the 1,3-propanediol (8c) was the
hydride source and propose a reaction mechanism as
summarized in Scheme 1.
The acetal formation easily takes place in the presence
of a catalytic amount of Sc(OTf)3 in an early stage of the
reaction. Sc(OTf)3 coordinates to the oxygen atom of the
acetal ring and then activates the acetal carbon even in
the presence of water. The activated acetal carbon
undergoes electrophilic aromatic substitution by an
aromatic compound followed by a ring scission of acetal
and then produces diphenylmethyl ether 11 as a key
intermediate. Sc(OTf)3 further coordinates the ethereal
oxygen of 11 and activates the benzylic carbon. The
ethereal bond of 11 successively is cleaved with simul-
taneous 1,3- or 1,5-hydride migration to furnish 3 and
3-hydroxypropanal (14).25,26
78
68c
78
9b
9c
7
8
99
95
51
89
82
86
33:4:63
18
17
20
20
17
15
9d
9e
9f
3p
3q
3r
quant 36:5:59
78 24:7:69
a
The reaction was carried out with 9 (1.0 mmol), 2 (5.0 mL),
and Sc(OTf)3 (0.05 mmol) at 125 °C. GLC yield. c The reaction
was carried out with 5.0 molar equiv of mesitylene in 1,2-
dichloroethane (5.0 mL) at the reflux temperature.
b
ger electron-releasing ability of the substituent.24 This
observation was also consistent with the typical electro-
philic aromatic substitution.
Sc(OTf)3-ca ta lyzed F r ied el-Cr a fts Alk yla tion Re-
a ction w ith Ar en eca r ba ld eh yd e Aceta ls. Since ac-
etalization reaction easily takes place in the presence of
a Lewis acid catalyst, the acetals derived from arenecar-
baldehydes 7 and 8c appears to be the crucial intermedi-
ate of the present benzylation reaction. If this hypothesis
is correct, the reductive Friedel-Crafts benzylation reac-
tion should be possible starting with arenecarbaldehyde
acetals 9.
Actually, Sc(OTf)3-catalyzed benzylation reaction of 2a
using 2-phenyl-1,3-dioxane (9a ) (eq 5) cleanly proceeded
to furnish 3a in a yield comparable to that of the one-
pot reaction (run 1, Table 7). Thus, the first stage of the
To obtain further insight into the reaction mechanism,
we heated a benzene solution of a mixture of benzalde-
hyde (7a ), 1,3-propanediol-1,1,3,3-d4 (8k ), and Sc(OTf)3
and were pleased to observe that deuterium was incor-
porated into the benzylic carbon of over 95% of the
diphenylmethane (3s) (eq 6). That the reaction with 2,4-
reaction may be the Sc(OTf)3-catalyzed acetalization of
arenecarbaldehyde 7. Indeed, the acetal formation was
confirmed by the reaction of 7a with 8c at ambient
temperature. Table 7 summarizes the reaction of various
9 with 2 in the presence of Sc(OTf)3 as a catalyst. As
readily seen, each reaction gave the corresponding 3 in
good to quantitative yields. The isomer ratios and the
dimethyl-2,4-pentanediol (8f) instead of 1,3-propane-
diol (8c) afforded a complex mixture of products is
another evidence for the hydride shift mechanism (run
7 in Table 4).
Diphenylmethyl ether 11 was separately prepared and
subjected to the reaction with 2a under the Friedel-
(24) (a) DeHaan, F. P.; Delker, G. L.; Covey, W. D.; Ahn, J .;
Anksman, M. S.; Brehm, E. C.; Chang, J .; Chicz, R. M.; Cowan, R. L.;
Ferrara, D. M.; Fong, C. H.; Harper, J . D.; Irani, C. D.; Kim, J . Y.;
Meinhold, R. W.; Miller, K. D.; Roberts, M. P.; Stoler, E. M.; Suh, Y.
J .; Tang, M.; Williams, E. L. J . Am. Chem. Soc. 1984, 106, 7038. (b)
DeHaan, F. P.; Chan, W. H.; Chang, J .; Cheng, T. B.; Chiriboga, D.
A.; Irving, M. M.; Kaufman, C. R.; Kim, G. Y.; Kumar, A.; Na, J .;
Nguyen, T. T.; Nguyen, D. T.; Patel, B. R.; Sarin, N. P.; Tidwell, J . H.
J . Am. Chem. Soc. 1990, 112, 356.
(25) The hydride ion transfer from alkoxy carbon of tetrahydro-
furan, 1,3-dioxolane, and 1,3-dioxepane to a trityl cation has been
reported. Din, K-u.; Plesch, P. H. J . Chem. Soc., Perkin Trans. 2 1987,
937.
(26) Oxidation product of alkyl group could not be detected because
it may undergo a condensation reaction to form polymeric products.

Scandium(III) Triflate-Catalyzed Alkylation Reactions
J . Org. Chem., Vol. 62, No. 20, 1997 7003
Sch em e 1
Crafts conditions (eq 7). Here again 3a was produced in
All experiments discussed above suggest a mechanism
in which the hydride source is the acetal moiety and
diphenylmethyl ether 11 is the most likely intermediate.
It should be noted that the reductive Friedel-Crafts
reaction involves initial acetal formation, carbon-carbon
bond formation, and subsequent intramolecular hydride
transfer. Each step is achieved effectively by the use of
a catalytic amount of Sc(OTf)3.
52% yield without contamination of triphenylmethane 15.
This observation suggests that 11 is a plausible inter-
mediate for the hydride shift process.27 The driving force
of the hydride shift should be the coordination of Sc(OTf)3
to the ethereal oxygen of 11, because 11 was recovered
in the absence of Sc(OTf)3. Furthermore, treatment of
Ph2CHOCH2CH2CH3 with a catalytic amount of Sc(OTf)3
similarly afforded 3a in 48% yield under the Friedel-
Crafts conditions, and the terminal hydroxyl group
appears not to be essential for the hydride shift process.
For the hydride shift, two routes are possible as depicted
in Scheme 1. At present, the 1,3-hydride shift pathway
is probable because of the experimental evidence.
The remaining possible pathway is the Friedel-Crafts
reaction of benzyl alcohol 1 which may be produced via
a bimolecular redox process between arenecarbaldehyde
7 and 1,3-propanediol (8c) through the Meerwein-
Ponndorf-Verley reaction. The in situ formation of the
benzyl alcohol, however, is not likely because no 4-chlo-
robenzyl alcohol (1c) was isolated in the reaction of
4-chlorobenzaldehyde (7d ) in a 1,2-dichloroethane, ni-
tromethane, or nitrobenzene solvent under the Friedel-
Crafts conditions (eq 8).
Con clu sion
We described here the Sc(OTf)3-catalyzed Friedel-
Crafts benzylation and allylation reaction with alcohols,
arenecarbaldehyde, or arenecarbaldehyde acetals as the
alkylating agent. The presently disclosed methods ap-
pear to be more practical and useful as compared with
the previously reported ones in view of the following
points.
(1) Friedel-Crafts reactions with alcohols as the alky-
lating agents are usually carried out under strictly
anhydrous conditions using considerably large quantities
of the Lewis acid catalyst. The presence of a small
amount of water lowers the yields drastically, because
the catalyst is rapidly decomposed or deactivated by the
moisture. On the other hand, the reaction by use of a
catalytic amount of Sc(OTf)3 allows us to use an alcohol
as the alkylating agent. This reaction also can be
performed in an undried solvent without any special care.
Although the reductive Friedel-Crafts reaction with an
arenecarbaldehyde as an alkylating agent in the presence
of a diol involves the formation of H2O at an early stage
of the reaction, a catalytic amount of Sc(OTf)3 is enough
to complete the reaction.
(2) The recovered Sc(OTf)3 was shown to retain its
catalytic activity of benzylation of benzene with benzyl
(27) Effenberger, F.; Gu¨nther, G.; Ba¨uerle, P. Chem. Ber. 1992, 125,
941.

7004 J . Org. Chem., Vol. 62, No. 20, 1997
Tsuchimoto et al.
1
2834, 2936, 3027 cm-1; H NMR (200 MHz, CDCl3) δ 3.60-
4.10 (m, 8H), 6.60-7.40 (m, 8H); 13C NMR (CDCl3) δ 35.8, 41.4,
55.6, 55.7, 55.8, 60.3, 110-153 (additional several peaks). Anal.
Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C, 79.14; H,
7.09.
alcohol. Sc(OTf)3 can be repeatedly employed, and di-
phenylmethane was obtained uniformly in high yields:
91% yield in the first run, 89% yield in the second run,
84% yield in the third run, respectively.
(3) We found that Sc(OTf)3 catalyzed the reductive
Friedel-Crafts reaction using an arenecarbaldehyde
acetal as the alkylating agent. This reaction is concluded
to proceed through a redox process involving a hydride
shift from the glycoholic moiety to the benzylic carbon.
(4) In almost all cases, the reactions proceed smoothly
to furnish the corresponding alkylation products in
excellent to quantitative yields using a catalytic amount
of Sc(OTf)3.
Sc(OTf)3-Ca ta lyzed Allyla tion Rea ction of Allyl Alco-
h ol w ith Ben zen e. A Typ ica l Exp er im en ta l P r oced u r e.
A 50-mL two-necked round-bottomed flask, fitted with a reflux
condenser, was charged with Sc(OTf)3 (0.050 g, 0.1 mmol) and
2a (5.0 mL). To this suspension of Sc(OTf)3 was added 5a (58.0
mg, 1.0 mmol) at ambient temperature. The mixture was
vigorously stirred at the reflux temperature for 8 h, treated
with H2O, and extracted with diethyl ether (10 mL) three
times. The combined extracts were then dried over MgSO4.
GC/MS analysis exhibited the presence of 6a , the yield of
which was estimated to be 48% using naphthalene as the
internal standard. All of the products are known compounds
and were characterized by a comparison of their spectral data
with those of authentic samples unless otherwise noted.29
RE(OTf)3 is an ideal and promising catalyst to solve
troublesome environmental problems caused by the Lewis
acid-promoted reactions used for industrial processes.
Sc(OTf)3-Ca t a lyzed Ben zyla t ion R ea ct ion of Ar en e-
ca r ba ld eh yd es w ith Ar en es in th e P r esen ce of 1,3-
P r op a n ed iol. A Typ ica l Exp er im en ta l P r oced u r e. A 50-
mL two-necked round-bottomed flask, fitted with a reflux
condenser, was charged with Sc(OTf)3 (0.050 g, 0.1 mmol). The
flask was heated at 180 °C in vacuo overnight. The flask was
cooled down to room temperature and then was successively
charged with 2b (5.0 mL), 8c (84 mg, 1.1 mmol), and 7d (141
mg, 1.0 mmol) at room temperature with stirring. The whole
mixture was heated at reflux temperature for 18 h under
stirring, cooled to room temperature, and poured into H2O.
The organic phase was separated, and the aqueous phase was
extracted with diethyl ether. The combined organic extracts
were dried over MgSO4. A GC/MS analysis revealed the
presence of an isomeric mixture of 3o, each amount being
determined with naphthalene as the internal standard. The
isomer ratio of the ortho-, meta-, and para-substituted diaryl-
methanes was estimated by GC, and the retention times were
compared with those of the authentic samples.14 All of the
products are known compounds and were characterized by a
comparison of their spectral data with those of authentic
samples unless otherwise noted.14,23
Exp er im en ta l Section
Gen er a l. 1H and 13C NMR spectra were recorded in CDCl3,
and the chemical shifts are reported in δ units downfield from
Me4Si as an internal standard. Gas chromatography analyses
were carried out using a capillary column (DB-5-30N-STD,
J &W Scientific, 0.25 mm, 30 m) and helium as the carrier gas.
Elemental analyses were carried out at the Elemental Analysis
Center, Tokyo Institute of Technology. For thin layer chro-
matographic (TLC) analyses throughout this work, Merck
precoated TLC plates (silica gel 60 PF254, 0.25 mm) were used.
Silica gel column chromatography was performed using Merck
Kieselgel 60 (70-230 mesh). Flash column chromatography
was performed using Merck Kiesegel 60 (230-400 mesh).
Ma ter ia ls. Sc(OTf)3 was purchased from Aldrich Chemical
Inc. and used without purification. Y(OTf)3, Nd(OTf)3, Sm(OTf)3,
and Yb(OTf)3 were prepared from the corresponding RE2O3
(Nippon Yttrium Co., Ltd., 99.9%) and TfOH (Central Glass
Co., Ltd.) in water according to the literature procedure;5 the
resulting hydrates were dried by heating under vacuum at 200
°C for 48 h. Benzene, toluene, p-xylene, mesitylene, and
anisole were distilled under an argon atmosphere from sodium/
benzophenone ketyl right before use. 1,2-Dichloroethane,
chloroform, nitromethane, and dichloromethane were distilled
under an argon atmosphere from calcium hydride right before
use. All of the aldehydes and alcohols are commercially
available and purified by distillation under reduced pressure
before use. Authentic samples of substituted diarylmethanes
for the GC/MS analyses were prepared by the Lewis acid-
catalyzed Friedel-Crafts benzylation of the substituted benzyl
chloride or benzyl bromide with arenes.14
Sc(OTf)3-Ca ta lyzed Ben zyla tion Rea ction of Ben zyl
Alcoh ol w ith Ar en es in th e P r esen ce of 1,3-P r op a n ed iol.
A Typ ica l Exp er im en ta l P r oced u r e. A 50-mL two-necked
round-bottomed flask, fitted with a reflux condenser, was
charged with Sc(OTf)3 (0.050 g, 0.1 mmol) and 2a (5.0 mL).
To this suspension of Sc(OTf)3 was added 1a (0.108 g, 1.0
mmol) at ambient temperature. The mixture was vigorously
stirred at the reflux temperature for 6 h, treated with H2O (2
mL), and extracted with diethyl ether (10 mL) three times.
The combined extracts were dried over MgSO4. GC/MS analy-
sis exhibited the presence of 3a , compared with authentic
sample. The yield of 3a was estimated to be 91% using
naphthalene as an internal standard.14 Most of the products
are known compounds and were characterized by a comparison
of their spectral data with those of authentic samples unless
otherwise noted.14,23,27
P r ep a r a tion of Ar en eca r ba ld eh yd e Aceta ls. Cyclic
acetals of arenecarbaldehydes were prepared by the acid-
catalyzed acetalization with the corresponding diol.31 The
following procedure is typical. A two-necked, round-bottomed
flask, equipped with a Dean-Stark trap, is charged with a
mixture of 7b (2.4 g, 20 mmol), 8c (1.9 g, 25 mmol), p-
toluenesulfonic acid (40 mg), and benzene (100 mL). The
solution was heated at reflux with stirring until no further
water separated. The solution was then cooled to room
temperature. Triethylamine (1.0 mL) was added to the
reaction mixture, which was then partitioned between diethyl
ether and water. The organic phase was washed with 10%
sodium hydroxide (20 mL) and then with brine and dried over
K2CO3. Evaporation of the solvent gave practically pure 9b,
which was purified by recrystallization from pentane (3.5 g,
19.7 mmol, 98% yield). All of the arenecarbaldehyde acetals
are known compounds and were characterized by a comparison
of their spectral data with those of authentic samples unless
otherwise noted.23
1,1,3,3-Tetr a d eu ter io-2-eth yl-1,3-p r op a n ed iol (8k ).23
A
50-mL two-necked round-bottomed flask, fitted with a drop-
ping funnel and a reflux condenser connected with an argon
line, was charged with lithium aluminum deuteride (949 mg,
25 mmol) and diethyl ether (20 mL). The mixture was heated
to reflux for 30 min and then cooled to room temperature. A
solution of diethyl ethylmalonate (3.8 g, 20 mmol) dissolved
in diethyl ether (20 mL) was added slowly with stirring at such
Spectral and analytical data of new compounds prepared
follow.
(Dim eth oxyp h en yl)p h en ylm eth a n e (3f).28 This com-
pound was obtained as a ca. 1:1 regioisomeric mixture by the
reaction of 2f with 1a : bp 135 °C/0.4 mmHg (Kugelrohr
distillation); IR (neat) 700, 1030, 1080, 1140, 1154, 1237, 1262,
(29) The allylation products were identified by comparison to their
spectral data with those of authentic samples. (a) Alexakis, A.; Cahiez,
G.; Normant, J . F. Synthesis 1979, 826. (b) Hayashi, T.; Konishi, M.;
Yokota, K.; Kumada, M. J . Organometal. Chem. 1985, 285, 359. (c)
Zadok, E.; Rubinraut, S.; Mazur, Y. J . Org. Chem. 1987, 52, 385.
(30) Roelofsen, D. P.; van Bekkum, H. Synthesis 1972, 419.
(28) Bandaranayake, W. M.; Riggs, N. V. Aust. J . Chem. 1981, 34,
115.
(31) Napolitano, E.; Fiaschi, R.; Mastrorilli, E. Synthesis 1986, 122.

Scandium(III) Triflate-Catalyzed Alkylation Reactions
J . Org. Chem., Vol. 62, No. 20, 1997 7005
a rate that the solvent continued to reflux gently. After the
addition was completed, the mixture was stirred at the reflux
temperature for an additional 3 h. The mixture was cooled to
room temperature, and the excess deuteride was decomposed
by slow addition of saturated sodium sulfate solution. The
insoluble material was filtered and washed fully with chloro-
form. The combined filtrate was dried over MgSO4 and
concentrated to give a crude product, which was purified by
flash chromatography, using hexane-diethyl ether (1/1) to
afford the diol (984 mg, 46%) as an oil. 8k was characterized
by a comparison of the spectral data with that of an authentic
sample.23
Sc(OTf)3-Ca ta lyzed Rea ction of Ar en eca r ba ld eh yd e
Aceta ls w ith Ar en es. A Typ ica l Exp er im en ta l P r oce-
d u r e. A 50-mL two-necked round-bottomed flask, fitted with
a reflux condenser, was charged with Sc(OTf)3 (0.050 g, 0.1
mmol). The flask was heated at 180 °C in vacuo overnight.
The flask was then cooled to room temperature and succes-
sively charged with 2b (5.0 mL) and 9c (199 mg, 1.0 mmol).
The mixture was stirred at reflux temperature for 17 h, cooled,
and poured into H2O. The organic phase was separated, and
the aqueous phase was extracted with diethyl ether. The
combined organic extracts were dried over MgSO4. GC/MS
analysis revealed the crude 3o contained (4-chlorophenyl)(p-
tolyl)methane, (4-chlorophenyl)(o-tolyl)methane, and (4-chlo-
rophenyl)(m-tolyl)methane; each product was compared with
the authentic sample,14 and the yield and isomer ratio were
determined using naphthalene as the standard.
3-Hyd r oxyp r op yl Dip h en ylm eth yl Eth er (11).23 This
ether was prepared by the reduction of 2,2-diphenyl-1,3-
dioxane with LiAlH4-AlCl3. The general experimental pro-
tocols followed in this study parallel those described in the
literature.32
Ack n ow led gm en t. S.F. acknowledges a Grant-in-
Aid for Scientific Research on Priority Areas “New
Development of Rare Earth Complexes” from the Min-
istry of Education, Science, Sports and Culture. We are
also grateful to the Asahi Glass Foundation for financial
support and Central Glass Co., Ltd. for kindly supplying
us with TfOH.
J O970599U
(32) Eliel, E. L.; Badding, V. D.; Rerick, M. N. J . Am. Chem. Soc.
1962, 84, 2371.