Preparation of 2-trimethylsilylmethyl-1-alkene; cross-coupling and protodesilylation sequence from 1,1-dibromo-1-alkene

Article abstract of DOI:10.1016/j.tetlet.2006.12.044

A new method for the preparation of exomethylene type allylsilane is described. Selective mono-protodesilylation of 1-trimethylsilyl-2-trimethylsilylmethyl-2-alkenes 2 with PPTS afforded 2-trimethylsilylmethyl-1-alkenes 4 in excellent yields. Since the resulting allylsilanes 4 possess an exomethylene unit, the reactions of 4 with carbonyl compounds in the presence of Lewis acids gave the corresponding product 7 having an exomethylene unit in excellent yields.

Full text of DOI:10.1016/j.tetlet.2006.12.044

Tetrahedron Letters 48 (2007) 1237–1240
Preparation of 2-trimethylsilylmethyl-1-alkene; cross-coupling
and protodesilylation sequence from 1,1-dibromo-1-alkene
Jun’ichi Uenishi,* Takuya Iwamoto and Masashi Ohmi
Kyoto Pharmaceutical University, Misasagi Yamashina, Kyoto 607-8412, Japan
Received 15 November 2006; revised 6 December 2006; accepted 11 December 2006
Abstract—A new method for the preparation of exomethylene type allylsilane is described. Selective mono-protodesilylation of 1-
trimethylsilyl-2-trimethylsilylmethyl-2-alkenes 2 with PPTS afforded 2-trimethylsilylmethyl-1-alkenes 4 in excellent yields. Since the
resulting allylsilanes 4 possess an exomethylene unit, the reactions of 4 with carbonyl compounds in the presence of Lewis acids gave
the corresponding product 7 having an exomethylene unit in excellent yields.
Ó 2007 Elsevier Ltd. All rights reserved.
R
Allylsilane is one of the most useful functional groups
for carbon–carbon bond forming reactions.1 Allylsilanes
can be conventionally prepared and reacted with
aldehyde, ketone, enone and other electrophiles in the
presence of Lewis acid. However, protodesilylation
sometimes occurs as an undesirable side reaction in
Lewis acid promoted carbon–carbon bond formation
reactions (Scheme 1).2,3
R'
Hosomi-Sakurai
reaction
R'CH(OMe)
2
.
OMe
R
BF3 Et2O
SiMe
(ref. 4)
3
R'
R'
R'CHO
SiMe
R
R
3
+
3
OH
OH
3'
Lewis acid
SiMe
SiMe
3
2
3
We have recently reported the synthesis of 1-trimethylsil-
yl-2-trimethylsilylmethyl-2-alkene 2 from 1,1-dibromo-
1-alkene 1 by tandem Pd-catalyzed cross-coupling
reaction with silylmethyl Grignard reagents.4 Although
Lewis-acid promoted reactions of 2 with dimethyl acetal
using BF3ÆEt2O provided the corresponding homoallylic
alcohol methyl ether in good yields, those with an alde-
hyde gave complex mixtures including two kinds of
homoallylic alcohols 3 and 30 with other by-products.
Compound 3 is the result of 2 subjected to the
Hosomi–Sakurai reaction. The formation of 30 resulted
from the Hosomi–Sakurai reaction of exomethylene
other
+
by products
Acid
R
R
+
SiMe
3
4'
4
Scheme 2.
type allylsilane 4 with aldehyde (Scheme 2). Apparently,
4 was generated in the reaction mixture by the acid
promoted protodesilylation of 2. The acid treatment of
2 gave a mixture of 4 and the further protodesilylated
product 40. We considered that if the protodesilylation
of 2 could be controlled at the stage of mono-protodesilyl-
ation giving 4 selectively, then it would become a nice
3-step sequence for the preparation of exomethylene-type
allylsilane 45 from aldehyde via 1,1-dibromo-1-alkene
and 2, as shown in Scheme 3. In fact, we have used this
procedure for the total synthesis of (ꢀ)-laulimalide.6
However, its generality and versatility have not been
revealed.
E
Lewis acid
E
SiMe
3
R
R
R
Protodesilylation
Product
Scheme 1.
*
Corresponding author. E-mail: juenishi@mb.kyoto-phu.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.12.044

1238
J. Uenishi et al. / Tetrahedron Letters 48 (2007) 1237–1240
Tandem
Cross-coupling
Protodesilylation
R'
R'
R'
R'
CBr
4
Me SiCH MgCl
PPTS, rt
R'
3
2
Br
R
O
PPh
3
SiMe
R
R
cat.Pd(OAc)2, PPh3
3
R
THF:CH CN
(9:1)
3
R
Br
THF, 50 ºC
SiMe
3
SiMe
3
1a-f
4a-f
2a-f
4'a-f
a,
R = phenethyl, R' = H
R = nC , R' = H
H
b,
c,
d,
10 21
R = cyclohexyl, R' = H
R = 1-phenethy, R' = H
e, R = phenyl, R' = H
t
f,
R = R' = -(CH ) -CH Bu-(CH ) -
2 2
2 2
Scheme 3.
In this Letter, we report an acid-promoted protodesilyl-
ation of bisallylsilanes 2 for the general preparation of
2-trimethylsilylmethyl-1-alkenes 4 and synthetic utilities
of the allylsilanes for efficient coupling with some
though undesired reactions occurred partially in the
cases of 2e and 2f (Table 1). Protodesilylated products
4 or 40 were obtained not only by Lewis acid but also by
Bro¨nsted acid promoted electrophilic reactions. Proto-
desilylation of 2a with aq HCl in THF gave a mixture
of 2a, 4a and 40a. The reaction was conducted in a mix-
ture of acetic acid/THF/H2O = 3:2:1 ratio for 2.5 h at
room temperature and gave a mixture of 4a and 40a in
a 2:1 ratio. The use of ZnCl2 in CH2Cl2 for 30 min at
room temperature gave them in a 26:2:1 ratio, and IR-
400 resin in CH2Cl2 gave a recovery of 2a. However,
when 1 equiv of PPTS was used in THF for 4 h at room
temperature, the reaction gave a 1:5:0 ratio of 2a:4a:40a.
electrophiles, giving compounds
exomethylene.
7 that have an
A 1,1-dibromo-1-alkene 1 can be derived from the
corresponding aldehyde or ketone with carbon tetra-
bromide and triphenylphosphine.7 The Pd-catalyzed
tandem Kumada–Tamao–Corriu cross-coupling reac-
tion of 1a–d with an excess of trimethysilylmethyl Grig-
nard reagent gave 2a–d in good to excellent yields,8
Table 1. Preparation of 2-trimethylsilylmethyl-1-alkene from aldehydes and ketones
Entry
1,1-Dibromo-1-alkene 1
Yielda (%)
Bisallylsilane 2
Yielda (%)
93
Allylsilane 3
Yielda (%)
97
Br
Ph
SiMe
Ph
3
Ph
1
1a
88
2a
4a
Br
SiMe
3
SiMe
3
Br
SiMe
3
7
7
2
3
4
1b
1c
1d
95
92
96
2b
2c
2d
94
85
79
4b
4c
4d
Quant.
Quant.
96
7
Br
SiMe
SiMe
3
3
Br
Br
SiMe
3
SiMe
SiMe
3
3
SiMe
3
Br
Br
SiMe
3
SiMe
SiMe
3
Br
Br
3
5
6
1e
1f
98
95
2e
2f
43b
21d
4e
4f
85c
26
SiMe
SiMe
3
3
SiMe
3
Br
Br
SiMe
3
tert
Bu
SiMe
tert
Bu
3
tert
Bu
a Isolated yield.
b Polymer was formed.
c 2 days.
d 4-tert-Butyl-1-(2-trimethylsilylvinyl)cyclohexane was a major by-product.

J. Uenishi et al. / Tetrahedron Letters 48 (2007) 1237–1240
1239
The reaction in CH3CN and MeOH is faster than that in
Lewis acid
Ph
E
4a
THF. Eventually, when the reaction was performed in a
9:1 mixture of THF:CH3CN, 4a was obtained exclu-
sively in a 97% yield.9 An addition of MeOH, CH3CN
or CH2Cl2 to THF accelerates the reaction.
Electrophile
+
( E )
7a-f
a,
E = -CH(OH)Ph
i
b, E = -CH(OH) Pr
Other results for the synthesis of 4 from carbonyl com-
pound in three steps are listed in Table 1. Protodesilyl-
ation of 2 takes place very nicely with PPTS in a mixed
solvent of THF and CH3CN or MeOH with the excep-
tion of 2f.10 In the case of ketone (entry 6), the forma-
tion of 2f and its protodesilylation were both
troublesome. The protodesilylation of 2f was slow and
the starting material was recovered along with decom-
posed products. The use of a stronger acid or harsh
conditions gave disappointing results in the protodesilyl-
ation reaction.11
c,
E = -CH(OMe)Ph
i
d, E = -CH(OMe) Pr
OH
e,
E =
O
f, E =
Scheme 5.
Table 2. Lewis-acid promoted reaction of 4a with various electrophiles
Although compounds 2 were yielded by the tandem Pd-
catalyzed cross-coupling directly from 1, Ni-catalyzed
cross-coupling reaction of 1a with TMSCH2MgCl in
ether at room temperature gave 2-bromo-5-phenyl-1-tri-
methylsilyl-2-pentene 5 in an 89% yield (Scheme 4). Pro-
todesilylation of 5 was performed with TiCl4 in CH2Cl2
at ꢀ78 °C to give 2-bromo-5-phenyl-1-pentene 6 in an
87% yield. Vinylbromide 6 is known as a vinyl anion
equivalent. Thus, after a metal–bromine exchange reac-
tion, the corresponding vinyl-metal can react with
various electrophiles to give coupling products that have
Entry Electrophile
Lewis acid Product Yield (%)
a
1
2
3
4
PhCHO
iPrCHO
InCl3
InCl3
7a
7b
7c
7c
88
80
75
75
b
PhCHO(OMe)2 BF3ÆOEt2
iPhCHO(OMe)2 BF3ÆOEt2
O
c,d
5
TiCl4
7e
96
O
c,e
an exomethylene unit. The introduction of
a
6
TiCl4
7f
69 (1,4-adduct)
trimethylsilylmethyl group to 6 by Pd-catalyzed cross-
coupling with TMSCH2MgCl gave 4a in an 88% yield.
a 0.2 equiv in CH2Cl2 at 0 °C for 2.5 h.
b 1.2 equiv in CH2Cl2 at ꢀ78 °C to rt for 30 min.
Next, allylsilane 4a was subjected to further carbon–car-
bon bond formation with aromatic and aliphatic alde-
hyde, their acetals, cyclohexanone and cyclohexenone
in the presence of Lewis acid. The results are shown in
Scheme 5 and Table 2. In all cases, an exomethylene
product 7 was obtained. The Hosomi–Sakurai reaction
of 4a with aldehydes and acetals was conducted using
InCl3 at 0 °C and using BF3ÆOEt2 at ꢀ78 to 0 °C giving
7a–d in good to excellent yields. TiCl4 promoted addi-
tion with cyclohexanone gave 7e in a 96% yield. On
the other hand, the reaction of 4a with cyclohexenone
gave 1,4-adduct 7f in a 69% yield.
c 1.2 equiv in toluene at ꢀ78 °C.
d 2 h.
e 5 min.
Br
R
R
SiMe
3
4
6
allyl anion equivalent
R
vinyl anion equivalent
R
In conclusion, a new preparation of allylsilanes 4 has
been achieved by tandem cross-coupling of 1 and selec-
Figure 1.
tive protodesilylation of 2. Compounds 4 have an exo-
methylene unit regarded as an allyl anion equivalent
that reacts with various electrophiles to produce addi-
tion products featuring an exomethylene unit (Fig. 1).
Compound 4a was also prepared from 1a by stepwise
cross-coupling through compounds 5 and 6. Compound
6 is also useful as a vinyl anion equivalent for the synthe-
sis of compounds possessing an exomethylene unit.
Me SiCH MgCl
3
2
cat. NiCl (dppp)
2
Ph
SiMe
3
1a
ether, rt
Br
89%
5
Protodesilylation
Me SiCH MgCl
3
2
cat. Pd(OAc)2, PPh3
TiCl
4
Ph
4a
Acknowledgements
THF, rt
CH2Cl2
Br
-78 ºC
6
87%
This work was supported by Grant-in-Aid for Scientific
Research on Priority Areas 17035084 and by the 21st
Scheme 4.

1240
J. Uenishi et al. / Tetrahedron Letters 48 (2007) 1237–1240
6. Uenishi, J.; Ohmi, M. Angew. Chem., Int. Ed. 2005, 44,
2756.
7. (a) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13,
3769; (b) Ramirez, F.; Desai, N. B.; McKelvie, N. J. Am.
Chem. Soc. 1962, 84, 1745.
COE Program from Ministry of Education, Culture,
Sports, Science and Technology, Japan.
8. The synthesis and chemistry of bisallylsilane see: (a)
Kercher, T.; Livinghouse, T. J. Org. Chem. 1997, 62, 805;
(b) Wang, K. K.; Yang, K. E. Tetrahedron Lett. 1987, 28,
1003; (c) Wang, K. K.; Dhumrongvaraporn, S. Tetra-
hedron Lett. 1987, 28, 1007, Typical experiment: To a
mixture of Pd(OAc)2 (0.1 mmol) and 1 (1 mmol) in THF
(10 mL) was added PPh3 (0.2 mmol) and the mixture was
stirred for 10 min at room temperature. Me3SiCH2MgCl
(2.5 mL, 1 M solution in Et2O) was added at 0 °C and the
mixture was stirred for 2–12 h at room temperature. After
quenching with satd NH4Cl, extraction with hexane and
purification by silica gel column chromatography gave
bisallylsilane 2.
9. Typical experiment: A mixture of 2 (1 mmol) and PPTS
(1.5 mmol) was stirred in a mixture of THF (9 mL) and
CH3CN (1 mL) at room temperature overnight. Then the
mixture was quenched with aq NaHCO3 and extracted
with hexane. The crude product was purified by column
chromatography on silica gel to give 4.
References and notes
1. Reviews of Hosomi–Sakurai reaction: (a) Fleming, I.;
Dunogues, J.; Smithers, R. Org. React. 1989, 37, 57; (b)
Fleming, I. Allylsilanes, Allylstannanes and Related Sys-
tems. In Comp. Org. Synth.; Trost, B. M., Fleming, I.,
Eds.; Pergamon Press: Oxford, 1991; Vol. 2, p 563.
2. Protodesilylation as a side reaction, for example: Schinzer,
D.; Allagiannis, C.; Wichmann, S. Tetrahedron 1988, 44,
3851.
3. Studies of protodesilylation of allylsilanes: (a) Fleming, I.;
Higgins, D. J. Chem. Soc., Perkin Trans. 1 1998, 2673, and
references cited therein; The mechanism of protodesilyl-
ation: (b) Hayashi, T.; Ito, H.; Kumada, M. Tetrahedron
Lett. 1982, 23, 4605; (c) Fleming, I.; Marchi, D.; Patel,
S. K. J. Chem. Soc., Perkin Trans. 1 1981, 518.
4. Uenishi, J.; Ohmi, M. Heterocycles 2003, 61, 365.
5. The previous preparation of exomethylene allylsilanes: (a)
Narayanan, B. A.; Bunnelle, W. H. Tetrahedron Lett.
1987, 28, 6261; (b) Lee, T. V.; Porter, J. R.; Roden, F. S.
Tetrahedron Lett. 1988, 29, 5009; (c) Saulnier, M. G.;
Kadow, J. F.; Tun, M. M.; Langley, D. R.; Vyas, D. M.
J. Am. Chem. Soc. 1989, 111, 8320.
10. It should be noted that protodesilylation is a delicate
reaction. Fine adjustment of reaction conditions for
solvent and temperature are required in specific cases.
11. Over protodesilylation occurred.