A convenient method for the synthesis of 4,4-diarylbut-1-enes via the successive allylation of aromatic aldehydes and the Friedel-Crafts alkylation reaction of aromatic nucleophiles with the intermediary benzyl silyl ethers using HfCl4 or Cl2Si(OTf)2

Article abstract of DOI:10.1016/S0040-4039(02)01374-6

The three-component coupling reaction among aromatic aldehydes, allyltrimethylsilane and aromatic nucleophiles is efficiently performed by the promotion of HfCl₄. A similar reaction occurs using allyltributyltin as the first nucleophile to aromatic aldehydes with a catalytic amount of Cl₂Si(OTf)₂ generated in situ from SiCl₄ and AgOTf.

Full text of DOI:10.1016/S0040-4039(02)01374-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6395–6398
A convenient method for the synthesis of 4,4-diarylbut-1-enes via
the successive allylation of aromatic aldehydes and the
Friedel–Crafts alkylation reaction of aromatic nucleophiles with
the intermediary benzyl silyl ethers using HfCl4 or Cl2Si(OTf)2
Isamu Shiina,* Masahiko Suzuki and Kazutoshi Yokoyama
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601,
Japan
Received 30 May 2002; revised 1 July 2002; accepted 5 July 2002
Abstract—The three-component coupling reaction among aromatic aldehydes, allyltrimethylsilane and aromatic nucleophiles is
efficiently performed by the promotion of HfCl4. A similar reaction occurs using allyltributyltin as the first nucleophile to
aromatic aldehydes with a catalytic amount of Cl2Si(OTf)2 generated in situ from SiCl4 and AgOTf. © 2002 Elsevier Science Ltd.
All rights reserved.
In the preceding communication,1 the Friedel–Crafts
alkylation of aromatic compounds with benzyl or allyl
silyl ethers as versatile electrophiles to produce various
diarylmethanes was reported. As an application of the
novel reaction for the convenient synthesis of more
complex molecules, we planned to use homoallyl silyl
ethers A having a benzyl silyl ether moiety because A
are easily generated by the addition of allyltrimethyl-
silanes to aromatic aldehydes (Scheme 1).2 Since both
the allylation forming A and successive Friedel–Crafts
alkylation of aromatic nucleophiles with A could be
promoted under acidic conditions,1 a one-pot synthetic
method for the preparation of a variety of 4,4-diaryl-
but-1-enes B might be established by the successive
allylation and Friedel–Crafts alkylation reaction. We
would now like to report a new sequential reaction that
forms various substituted butenes B via the three-com-
ponent coupling reaction among aromatic aldehydes,
allylmetal reagents and aromatic compounds.
First, the isolated trimethylsilyl ether 1 was chosen as a
model substrate to examine the Friedel–Crafts alkyla-
tion (Table 1). Similar to results in the preceding com-
munication, the reaction of anisole with 1 smoothly
proceeded to give the desired disubstituted butenes 2 in
high yields when Cl2Si(OTf)2 or Hf(OTf)4 was used as
the catalyst. The reaction of anisole with 1 or the
corresponding free alcohol (1-phenylbut-3-en-1-ol) in
the presence of Sc(OTf)3 afforded the coupling products
in moderate or low yields (50 or 23%).
Table 1. Isolated yields of 4-methoxyphenyl-4-phenylbut-1-
enes
Entry
Catalyst
Time (h)
Yield (%)
(o-/p-)a
Scheme 1. Three-component coupling among aromatic alde-
hydes, allyltrimethylsilanes and aromatic nucleophiles.
1
2
3
Cl2Si(OTf)2
Hf(OTf)4
Sc(OTf)3
1
1
12
93
Quant.
50
20/80
19/81
20/80
* Corresponding author. Fax: (+81)-3-3260-5609; e-mail: shiina@
ch.kagu.sut.ac.jp
a Determined by 1H NMR.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01374-6

6396
I. Shiina et al. / Tetrahedron Letters 43 (2002) 6395–6398
Next, we tried to develop the three-component coupling
reaction using aromatic aldehydes, allyltrimethylsilanes
and aromatic nucleophiles in order to directly produce
2 by the one-pot operation; that is, after generation of
the benzyl silyl ether 1 in situ from benzaldehyde (1.0
equiv.) and allyltrimethylsilane (1.2 equiv.) using a cat-
alytic amount of Cl2Si(OTf)2 (20 mol%) in CH2Cl2,
anisole (5 equiv.) was added to the reaction mixture.
However, a regioisomeric mixture of the corresponding
cyclic ethers 3 was mainly obtained by the sequential
coupling of 1 with benzaldehyde followed by cycliza-
tion and alkylation with anisole (Table 2, entry 1).3 The
reactions using Hf(OTf)4 and Sc(OTf)3 gave complex
mixtures of several by-products, and TMSOTf did not
promote the desired successive reactions. Furthermore,
anisole was used as a solvent for the first step in order
to prevent the side reaction of 1 with an excess amount
of benzaldehyde; nevertheless, the selectivities were not
improved and undesirable results occurred as shown by
entries 2–5.
Table 4 shows examples of the three-component cou-
pling reaction forming several disubstituted butenes.
4-Tolualdehyde and 4-halogenated benzaldehydes were
successfully employed for the generation of benzyl silyl
ethers, and the sequential addition of anisole to the
intermediates afforded the desired compounds in high
yields (entries 2–6). Although 4-anisaldehyde has a low
reactivity for the reaction with allyltrimethylsilane and
the total yield is not satisfactory (entry 7), the desired
4,4-diarylbut-1-enes were obtained in good yields using
4-pivaloxybenzaldehyde as an electrophile for the reac-
tion (entry 8). Furthermore, when toluene was used as
the solvent in the above reaction, a mixture of the
desired disubstituted butenes was produced in moderate
yield by a one-pot operation with benzaldehyde,
allyltrimethylsilane and HfCl4 (entry 10).
A typical experimental procedure is described for the
reaction of benzaldehyde with allyltrimethylsilane in
anisole: to a suspension of hafnium tetrachloride (80.1
mg, 0.250 mmol) in anisole (3.8 mL) at 0°C were
successively added a mixture of allyltrimethylsilane
(34.2 mg, 0.300 mmol) and benzaldehyde (26.5 mg,
0.250 mmol) in anisole (1.2 mL). The reaction mixture
was stirred for 45 min at room temperature and then
saturated aqueous sodium hydrogencarbonate was
added. The mixture was extracted with diethyl ether,
and the organic layer was washed with brine, dried over
sodium sulfate. After filtration of the mixture and
evaporation of the solvent, the crude product was
purified by thin layer chromatography to afford a
mixture of 4-methoxyphenyl-4-phenybut-1-enes (58.7
mg, 99%, (o-)/(p-)=16/84) as a colorless oil.
It was postulated that a Lewis acid, which has a weaker
acidity, is more suitable for the above synthesis since
metal triflates have a sufficient activity to promote the
undesired reaction of 1 with benzaldehyde. Based on
this hypothesis, various metal chlorides were reexam-
ined for the one-pot reaction, and it was found that the
stoichiometric use of HfCl4 is the most effective for the
selective formation of 2 (Table 3). It is quite remarkable
that the side reaction of the produced intermediate, the
benzyl silyl ether 1, with the benzaldehyde to produce 3
does not take place at all when HfCl4 is used as the
catalyst in the above sequential reactions (entries 6–8).
Table 2. Isolated yields of 4-methoxyphenyl-4-phenylbut-1-enes and 2,6-diphenyl-4-methoxyphenyl(2H-3,4,5,6-tetra-
hydropyrans)
Entry
Catalyst
Solvent
Temp. (°C)
Yield
2 (o-/p-)b
3 (o-/p-)b
1
2
3
Cl2Si(OTf)2
Cl2Si(OTf)2
Hf(OTf)4
Sc(OTf)3
CH2Cl2
Anisole
Anisole
Anisole
Anisole
0
25 (19/81)
0
5 (20/80)
6 (19/81)
0
25 (38/62)
41 (38/62)
38 (40/60)
30 (38/62)
0
rt
rt
rt
rt
4
5a
TMSOTf
a A mixture of triarylmethanes 4 was obtained in 20% yield.
b The ratio was determined by 1H NMR.

I. Shiina et al. / Tetrahedron Letters 43 (2002) 6395–6398
6397
Table 3. Isolated yields of 4-methoxyphenyl-4-phenylbut-1-enes, 2,6-diphenyl-4-methoxyphenyl(2H-3,4,5,6-tetrahydropyrans)
and 4-chloro-2,6-diphenyl(2H-3,4,5,6-tetrahydropyran)
Entry
Catalyst (amount)
Conc. (M)
Yield (%)
3 (o-/p-)a
2 (o-/p-)a
5
1
2
3
4
5
6
7
8
AlCl3 (0.2)
GaCl3 (0.2)
SiCl4 (0.2)
SnCl4 (0.2)
TiCl4 (0.2)
HfCl4 (0.2)
HfCl4 (1.0)
HfCl4 (1.0)
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0
24 (39/61)
14 (40/60)
1 (ND)
9 (40/60)
10 (41/59)
0
2
3
2
3
10
0
26 (20/80)
6 (20/80)
2 (19/81)
3 (20/80)
53 (15/85)
87 (16/84)
99 (14/86)
0
0
0
0
a The ratio was determined by 1H NMR.
Table 4. Isolated yields of several 4,4-diarylbut-1-enes
desired 2 in 90% yield (see Table 5, entry 1). In this
protocol, the intermediate, a tin alkoxide, is too stable
for the second electrophilic substitution with anisole.
Therefore, transmetallation of tin to silicon was per-
formed by adding TMSCl, and the instantly generated
trimethylsilyl ether 1 might work as a reactive elec-
trophile to anisole for producing the desired three-com-
ponent coupling products. According to this one-pot
but stepwise method, it is not necessary to use the
second nucleophile as a solvent for the first allylation
reaction. Furthermore, this protocol prevents forming
several by-products in principle since aromatic alde-
hydes do not contact the anisole or benzyl silyl ether 1
if the allylation completely proceeds. Other examples
are listed in Table 5. Similar results were obtained to
that of the three-component coupling reaction of aro-
matic aldehydes, allyltrimethylsilane and anisole using a
stoichiometric amount of HfCl4. It is noteworthy that a
catalytic amount of the Lewis acid is required in this
alternative strategy employing allyltributyltin and silyl-
ation reagents.
Entry
Y
W
Yield (%)
(o-W)/(p-W)a
1
2
3
4
5
6
7
8
9
H
4-Me
4-F
4-Cl
4-Br
4-I
4-OMe
4-OPiv
3-OPiv
H
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
Me
99
79
80
87
86
81
31
86
88
51
16/84
9/91
14/86
15/85
13/87
10/90
0/100
8/92
22/78
15/85
10
a Determined by 1H NMR.
A typical experimental procedure is described for the
reaction of benzaldehyde with allyltributyltin and
anisole: to a suspension of silver trifluoromethanesul-
fonate (25.7 mg, 0.100 mmol) in dichloromethane (1.85
mL) at room temperature was added silicon tetra-
chloride (8.5 mg, 0.050 mmol) in dichloromethane (0.15
mL). After the reaction mixture had been stirred for 1
h, a mixture of allyltributyltin (248.3 mg, 0.750 mmol)
in dichloromethane (1.0 mL) and benzaldehyde (53.1
mg, 0.500 mmol) in dichloromethane (1.0 mL) were
successively added. The reaction mixture was stirred for
1 min and then a solution of chlorotrimethylsilane (81.5
mg, 0.750 mmol) in dichloromethane (1.0 mL) was
added. After the reaction mixture had been stirred for
10 min, anisole (1.0 mL, 8.6 mmol) was added. The
reaction mixture was stirred for 2 h and then saturated
Next, allyltributyltin2 was used as the nucleophile
instead of allyltrimethylsilane for the three-component
coupling reaction with benzaldehyde and anisole. After
screening several catalysts, it was proved that HfCl4 (1
equiv.) does not have enough activity for the promotion
of the allylation of benzaldehyde with allyltributyltin
and the desired 4,4-diarylbut-1-enes 2 and the undesired
triarylmethanes 4 were produced in 30 and 62% yields,
respectively. On the other hand, it was found that the
allylation was efficiently promoted using the combined
catalyst generated in situ from 10 mol% SiCl4 and 20
mol% AgOTf, and the successive treatment of the
formed tin alkoxide with TMSCl and anisole gave the

6398
I. Shiina et al. / Tetrahedron Letters 43 (2002) 6395–6398
Table 5. Isolated yields of several 4,4-diarylbut-1-enes
methoxyphenyl-4-phenybut-1-enes (107.3 mg, 90%, (o-)/
(p-)=15/85) as a colorless oil.
Thus, we developed a new method for the one-pot
synthesis of 4,4-diarylbut-1-enes via the successive allyl-
ation of aromatic aldehydes and the Friedel–Crafts
alkylation reaction of aromatic nucleophiles with the
intermediary benzyl silyl ethers using HfCl4 or
Cl2Si(OTf)2. Other applications of the present protocol
and syntheses of useful derivatives from 4,4-diarylbut-
1-enes are now in progress.
Acknowledgements
Entry
Y
X
Yield (%)
(o-MeO)/(p-MeO)a
This work was partially supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education,
Science, Sports and Culture, Japan.
1
2
3
4
5
6
H
Cl
Cl
OTf
OTf
OTf
OTf
90
68
80
86
87
63
15/85
9/91
14/86
13/87
9/91
4-Me
4-Cl
4-Br
4-I
References
3-OPiv
23/77
a Determined by 1H NMR.
1. Preceding communication. Shiina, I.; Suzuki, M. Tetra-
hedron Lett. 2002, 43, 6391–6394.
2. Fleming, I. In Comprehensive Organic Synthesis; Trost, B.
M.; Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 2, pp.
563–593.
3. (a) Yang, J.; Viswanathan, G. S.; Li, C.-J. Tetrahedron
Lett. 1999, 40, 1627–1630; (b) Yang, J.; Li, C.-J. Synlett
1999, 717–718.
aqueous sodium hydrogencarbonate was added. The
mixture was extracted with dichloromethane, and the
organic layer was washed with brine, dried over sodium
sulfate. After filtration of the mixture and evaporation
of the solvent, the crude product was purified by thin
layer chromatography to afford a mixture of 4-