Stereoselective synthesis of unsymmetrical conjugated dienes and trienes utilizing silacyclobutenes

Article abstract of DOI:10.1016/j.tetlet.2007.03.122

Treatment of the different kinds of alkynyl-substituted dialkynyldiarylsilanes with zirconocene-ethylene complex Cp₂Zr(CH₂{double bond, long}CH₂) followed by acidification with 3 N HCl gave regio- and stereoselectively the

Full text of DOI:10.1016/j.tetlet.2007.03.122

Tetrahedron Letters 48 (2007) 3671–3675
Stereoselective synthesis of unsymmetrical conjugated dienes and
trienes utilizing silacyclobutenes
Chung Keun Jin,a Toshiaki Yamada,a Shigeki Sano,a Motoo Shirob and
Yoshimitsu Nagaoa,*
aGraduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
bRigaku Corporation, 3-9-12 Matsubara-cho, Akishima-shi, Tokyo 196-8666, Japan
Received 27 January 2007; revised 16 March 2007; accepted 22 March 2007
Available online 25 March 2007
Abstract—Treatment of the different kinds of alkynyl-substituted dialkynyldiarylsilanes with zirconocene–ethylene complex
Cp2Zr(CH2@CH2) followed by acidification with 3 N HCl gave regio- and stereoselectively the corresponding silacyclobutenes in
good yields. Desilylation of the silacyclobutenes with tetrabutylammonium fluoride afforded stereoselectively unsymmetrical conju-
gated (1E,3E)-dienes and -trienes (R1 or R2 = 1-cyclohexenyl) in excellent yields.
Ó 2007 Elsevier Ltd. All rights reserved.
Conjugated dienes and polyenes are often found in the
structures of biologically active natural products.1 Ster-
eoselective synthesis of conjugated dienes is very impor-
tant both for their use in diene-containing natural
products and for their application to other reactions
such as Diels–Alder reactions2 and oxygen 1,4-cycload-
dition reactions.3 Thus, a number of methods for syn-
thesizing the conjugated dienes and polyenes have
been developed by exploiting various organometallic
compounds involving boron,4 silicon,5 copper,6 nickel,7
zirconium,8 and titanium9 atoms. In recent years,
Negishi and co-workers have explored and disclosed a
number of fascinating reactions utilizing zirconium
catalysts.10
alkynes to silenes11 or the reaction of silyl-substituted
alkynes with polysilanes.12
Recently, we established an efficient procedure for syn-
thesizing dialkynyldiarylsilanes bearing different kinds
of alkynyl groups,13 which seemed to be remarkably
useful for the synthesis of various conjugated dienes,
trienes, and other functional organosilicon molecules.
Herein we describe a novel procedure for synthesizing
unsymmetrical conjugated (1E,3E)-dienes and -trienes
involving the reaction of the different kinds of alkynyl-
substituted dialkynyldiarylsilanes with a zirconocene
complex Cp2Zr(CH2@CH2) (Takahashi reagent)8b,c
formed in situ from Cp2ZrEt2, followed by treatment
of the resulting silacyclobutenes with tetrabutylammo-
nium fluoride (TBAF), as shown in Scheme 1. We also
discuss two kinds of possible reaction mechanisms for
Several years ago, Takahashi and co-workers reported
an interesting zirconocene-mediated intramolecular
carbon–carbon bond formation between two identical
alkyn- yl groups in bis(alkynyl)silanes.8b,c However,
only bis(alkynyl)silanes bearing the same alkynyl groups
were exclusively employed for the desirable zirconocene-
mediated reactions, and thus treatment of the resulting
silacyclobutenes with CuCl afforded only symmetrical
conjugated dienes.8b,c In general, silacyclobutenes have
been synthesized by utilizing the cycloaddition of
EtMgBr
(2.5 equiv)
Cp2ZrCl2
Cp2Zr(CH2=CH2)
(1.25 equiv)
THF, -60 oC, 1 h
Ar1
R1
Si Ar2
Ar1
Ar2
Si
THF, -60 o
to rt, 2 h
C
Cp2Zr
R2
R1
R1
R2
A
1a-m
3 N HCl, rt
Ar1 Ar2
R1
Si
TBAF (2.2 equiv)
THF, rt, 1 h
R2
R2
3a-g
2a-m
Keywords: Dialkynyldiarylsilane; Zirconium complex; Silacyclobutene;
Scheme 1. A stereoselective synthesis of unsymmetrical conjugated
(E,E)-alkadienes via desilylation of silacyclobutenes.
Tetrabutylammonium fluoride; Conjugated diene.
*
Corresponding author. E-mail: ynagao@ph.tokushima-u.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.03.122

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C. K. Jin et al. / Tetrahedron Letters 48 (2007) 3671–3675
regioselective formation of zirconacyclobutene–silacyclo-
butene fused-ring intermediates A toward silacyclobut-
enes 2a–m.
over 1 h with stirring and then stirred for an additional
1 h to form a zirconacyclobutene–silacyclobutene fused-
ring intermediate A (R1 = Ph, R2 = n-Bu, Ar1 = Ph,
Ar2 = Tip).8b,c The crude intermediate was treated with
3 N HCl to afford exclusively a novel Z-phenylmethyl-
ene-silacyclobutene 2a (R1 = Ph, R2 = n-Bu, Ar1 = Ph,
Ar2 = Tip) in a stereo- and regioselective manner and
in 80% yield based on 1a (Table 1, entry 1). Other
new Z-type-methylene-silacyclobutenes 2b–m were also
To a solution of Cp2Zr(CH2@CH2) in THF, obtained
from the procedure of Takahashi,8b,c was added phen-
yl-(2,4,6-triisopropylphenyl(Tip))(butylethynyl)(phen-
ylethynyl)silane (1a) at ꢀ60 °C. The resulting mixture
was allowed to warm gradually to room temperature
Table 1. Stereo- and regioselective synthesis of silacyclobutene derivatives utilizing Takahashi’s procedure
Entry
Dialkynylsilane
Ar1
Ar2
Product
Yielda (%)
1
2
3
1a
1b
1c
Ph
Ph
Tmpc
Tipb
2a
2b
2c
80
67
85
Ph
Ar1 Ar2
Si
Tmpc
Tmpc
Ar1
Ar2
Ph
Ph
Si
Si
n-Bu
n
-Bu
Ph
Ar1 Ar2
Si
Ar1
Ar2
4
5
1d
1e
Ph
Ph
Tipb
Tmpc
2d
2e
69
51
4
4
4
Ar1 Ar2
Si
Ar1
Ar2
6
7
1f
1g
Ph
Ph
Tipb
Tmpc
2f
2g
83
82
Si
Si
Si
n-Bu
n
-Bu
4
Ar1 Ar2
Si
Ar1
Ar2
8
9
1h
1i
Ph
Ph
Tmpc
Tmpc
2h
2i
65
65
n
-Bu
Ar1 Ar2
Ar1
Ar2
Si
n-Bu
Ph
Ph
Ar1 Ar2
Si
Ar1
Ar2
Si
Si
Ph
10
11
1j
Ph
Ph
Tipb
2j
86
4
Ar1
Ar2
Ar1 Ar2
Si
1k
Tipb
2k-1
2k-2
78d
Ph
4
Ar1 Ar2
Ph
Si
4
Ph
Ar1 Ar2
Si
Ar1
Ar2
12
1l
Ph
Ph
Tmpc
Tmpc
2l
48
72
Si
Si
Ph
Ph
Ph
Ar1 Ar2
Si
Ar1
Ar2
13
1m
2m
5
5
a Isolated yields.
b Tip = 2,4,6-triisopropylphenyl.
c Tmp = 2,4,6-trimethylphenyl.
d A 1:1 (2k-1:2k-2) ratio was determined by 1H NMR (400 MHz, CDCl3) analysis.

C. K. Jin et al. / Tetrahedron Letters 48 (2007) 3671–3675
3673
Ar1 Ar2
Si
stereo- and regioselectively obtained in 48–86% yields
Ar1
Insertion
Route
R1
Si Ar2
based on 1b–m by the reactions described above (Table
1, entries 2–10, 12, and 13). In the case of 1k, an insep-
arable mixture of silacyclobutenes (2k-1 and 2k-2) was
obtained in 78% total yield with a 1:1 (2k-1:2k-2) ratio
(Table 1, entry 11). All results are summarized in Table
1. The structures of 2c and 2d were precisely determined
by X-ray crystallographic analyses, as shown in Figure
1.14
Ar1 Ar2
Si
Cp2Zr
R2
R1
R2
Zr
A
R1
Cp2
R2
Zr
5
or
Cp2
Ar1
Si Ar2
R2
4
Vinylidene
Route
Ar1
Si
Cp2Zr
R1
THF
Ar2
Cp2Zr
R1
B
Cp2Zr
Ar1 Ar2
Si
R2
Other products were reasonably assigned to be struc-
tures 2a,b and 2e–m based on their spectroscopic and
elemental analyses in comparison with those of 2c and
2d. Interestingly, we recognized that aromatic groups
occupied the R1 site in products 2a–h and 2l,m and that
the R1 group was cyclohexenyl in 2i.
6
R1
R2
Ar1 Ar2
Si
Ar1 Ar2
Si
1a m
-
R2
R2
5
R1
R1
5
Zr
Zr
Cp2
Cp2
R1 = Phenyl,
4-Pentylphenyl
-Butyl, -hexyl
Cyclohexenyl
7
8
R2
=
n
n
On the basis of the experimental results in Table 1, we
can now comment on the proposed mechanisms for
the formation of silacyclobutenes from bis(alkynyl)-
silanes by Takahashi and his co-workers.8b,c Although
Takahashi proposed two mechanisms, an insertion route
(4!5!A) and a vinylidene route (4!6!A) for the for-
mation of the zirconacyclobutene–silacyclobutene fused-
ring intermediates A (Scheme 2),8b,c the former must
involve carbocationic intermediates 7 or 8 to obtain A
or B. Because the benzylic carbocationic intermediates
(R1 = phenyl or 4-substituted phenyl groups) 8 are more
stable than the aliphatic carbocationic intermediates
(R2 = n-butyl, n-hexyl, and cyclohexenyl groups) 7 in
the insertion route, the resulting predominant intermedi-
ates should be B, rather than the observed intermediates
A, to afford silacyclobutenes 2a–m. Thus, the exclusive
products 2a–m may be obtained via the vinylidene
(4!6!A) route although there is no direct evidence of
the vinylidene mechanism.15 In the vinylidene route,
initial preferential replacement of ethylene ligand of
Cp2Zr(CH2@CH2) with a more electron-rich alkynyl
group than another alkynyl group in the molecule of
1a–m seems to be essential for differentiation between
two kinds of alkynyl groups in the same molecules.15
A
B
Ar1 Ar2
Si
R1
R2
Cp Zr
Ar1 Ar2
Si
Cp
R2
Zr
4
1a m
-
6
R1
Ar1 Ar2
Si
Cp
Cp
R1
R2
A
10
Cp Zr
Cp
9
Scheme 2. Plausible mechanisms for the formation of zirconacyclo-
butene–silacyclobutene fused-ring intermediates A.
However, in the silacyclobutenes formation of com-
pound 1k having similar phenyl-substituted ethynyl
groups, the replacement of ethylene ligand of
Cp2Zr(CH2@CH2) with an alkynyl group may be
equally performed at both of the alkynyl moieties of
1k to give a 1:1 mixture of 2k-1 and 2k-2. In the case
of compound 1j having the different kinds of phenyl-
substituted ethynyl groups, the preferential ligand
replacement reaction can be done at more electron-rich
Tmp-ethynyl moiety than the phenyl-ethynyl moiety to
give an exclusive product 2j in 86% yield. Two resonance
types of alkyne–zirconium complex 4 and 9 probably
due to a-anion and/or b-cation stabilization by the Si–
C bond would be converted to a carbene type intermedi-
ate 10,16 in which 1,2-alkyl shift may proceed to give
vinylidene zirconium complex 10 and then A.
Si
Si
2c
Finally, we achieved the highly stereoselective conver-
sion of silacyclobutenes 2a,b, 2d–j, and 2m into the
corresponding unsymmetrical conjugated (1E,3E)-
dienes and -trienes 3a–g in very high yields by utilizing
TBAF, as shown in Table 2. Namely, a solution of 2a
in THF was treated with a solution of a 2.2 mol equiv
of TBAF in THF at room temperature for 1 h to give
(1E,3E)-1-phenyl-1,3-octadiene 3a in 99% yield (Table
2, entry 1).17
Si
Si
2d
Similar treatment of other silacyclobutenes 2b,d,e, 2h–j,
and 2m with TBAF in THF at room temperature for 1 h
Figure 1. Computer-generated drawing derived from the X-ray coor-
dinates of compounds 2c and 2d.

3674
C. K. Jin et al. / Tetrahedron Letters 48 (2007) 3671–3675
Table 2. Synthesis of unsymmetrical conjugated dienes and trienes
Entry
Silacyclobutene
Ar1
Ar2
Product
Yielda (%)
1
2
2a
2b
Ph
Ph
Tipb
99
99
Ar1 Ar2
Ph
Ph
Si
Tmpc
n-Bu
3a
Ar1 Ar2
Si
3
4
2d
2e
Ph
Ph
Tipb
Tmpc
98
97
3b
4
4
Ar1 Ar2
Si
5
6
2f
2g
Ph
Ph
Tipb
92d
99d
3c
Tmpc
4
n-Bu
Ar1 Ar2
Si
7
8
2h
2i
Ph
Ph
Tmpc
Tmpc
98
96
3d
4
Ar1 Ar2
Si
3e
n-Bu
Ar1 Ar2
Si
Ph
Ph
9
2j
Ph
Ph
Tipb
96
97
3f
Ar1 Ar2
Si
5
10
2m
Tmpc
3g
5
a Isolated yields.
b Tip = 2,4,6-triisopropylphenyl.
c Tmp = 2,4,6-trimethylphenyl.
d Reaction time: 20 h.
afforded the corresponding conjugated (1E,3E)-dienes
and -trienes 3a,b, and 3d–g in 96–99% yields, respec-
tively (Table 2, entries 2–4 and 7–10). The reaction of
2f and 2g with TBAF in THF required 20 h to give
the same conjugated (1E,3E)-diene 3c in 92% and 99%
yields, respectively (Table 2, entries 5 and 6). The struc-
ture and geometry of all of the conjugated (1E,3E)-
dienes and -trienes 3a–g were reasonably assigned on
the basis of their spectroscopic [1H NMR (400 MHz,
CDCl3) JE-type = 14–16 Hz, JZ-type = 11–12 Hz] and ele-
mental analyses data.
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In conclusion, we have demonstrated that the reactions
of different kinds of alkynyl-substituted dialkynyldiaryl-
silanes with a zirconocene complex Cp2Zr(CH2@CH2)
proceeded stereo- and regioselectively to give new
types of silacyclobutene derivatives, which were treated
with TBAF to furnish the corresponding unsymmetrical
conjugated (1E,3E)-dienes and -trienes in excellent
yields.
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˚
ꢀ
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˚
˚
9.8361(3) A,
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