Preparation and synthetic utility of 2-methylselenomethyl allyl methyl selenide. A valuable precursor to 2-silylmethylallyllithiums

Article abstract of DOI:10.1055/s-1998-1915

3-Lithio-2-[silylmethyl]propenes, easily prepared from 3-methylseleno-2-[silylmethyl]propenes by the cleavage of the C-Se bond, are useful intermediates for the preparation of a variety of functionalised allylsilanes. These allylsilanes are interesting bu

Full text of DOI:10.1055/s-1998-1915

November 1998
SYNLETT
1219
Preparation and Synthetic Utility of 2-Methylselenomethyl Allyl Methyl Selenide. A Valuable
Precursor to 2-Silylmethylallyllithiums
Alain Krief *1, Willy Dumont1, István E. Markó*2, Fiona Murphy2, Jean-Christophe Vanherck2, Romain Duval2 , Thierry Ollevier2 and Ulrich Abel2.
1Laboratoire de Chimie Organique de Synthèse, Département de Chimie, Facultés Universitaires Notre-Dame de la Paix, 61 rue de Bruxelles,
B-5000 Namur, Belgium.
FAX: 32-81-724536, e-mail: alain.krief@fundp.ac.be
2Laboratoire de Chimie Organique, Département de Chimie, Université catholique de Louvain, Bâtiment Lavoisier, 1 Place Louis Pasteur,
B-1348 Louvain-la-Neuve, Belgium.
FAX: 32-10-472788, e-mail: marko@chor.ucl.ac.be
Received 27 April 1998
Abstract: 3-Lithio-2-[silylmethyl]propenes, easily prepared from 3-
methylseleno-2-[silylmethyl]propenes by the cleavage of the C-Se
bond, are useful intermediates for the preparation of a variety of
functionalised allylsilanes. These allylsilanes are interesting building
blocks, used for example, as annelating agents in the efficient synthesis
of spiroketals by the Intramolecular Silyl-Modified Sakurai (ISMS)
cyclisation. The methodology described in this article provides also an
expedient route to a range of heterosubstituted methylselenopropenes,
which are valuable precursors to a range of useful heterosubstituted
allyllithium reagents. Finally, a one-step preparation of functionalised
[trimethylsilylmethyl]propene 1a (Scheme 1), we decided to develop a
less expensive and more flexible route (Table 1, Entry 1) starting from
3-methylseleno-2-[methylselenomethyl]propene 7.[1] Addition of
1 equivalent of n-BuLi (THF, -78°C, 0.25h) smoothly generated the
allyllithium species 8 by selective cleavage of one of the C-Se bonds.
Subsequent trapping with a range of silylchlorides efficiently produced
a variety of substituted allylsilanes 2 in excellent overall yield (Table
1)[5]
.
3-Methylseleno-2-[triisopropylsilylmethyl]propene 2c proved to be
particularly acid sensitive and could only be purified by distillation after
washing the crude reaction mixture with a saturated solution of aqueous
sodium bicarbonate.
allylsilanes
from
readily
available
3-methylseleno-2-
[methylselenomethyl]propene is reported.
Table 1.
Preparation of substituted allylselenides
2
Some time ago, we reported the smooth reaction of 3-methylseleno-2-
[trimethylsilylmethyl]propene 2a with butyllithium to produce the
lithiated allylsilane 3a (Scheme 1).[1]
R1
R3
R1
R2
R3
SeMe
Si
Si
Li
SeMe
R2
Cl
n-BuLi
This valuable intermediate has since been used for the synthesis of
various annelating agents such as 5 required for the Intramolecular Silyl
Modified Sakurai (ISMS) reaction. Condensation of silyl ether 5 with
ortholactones has been shown to provide an efficient approach to
spiroketals (Scheme 1).[1] This flexible methodology has been applied
to the synthesis of several natural products including insect pheromones
and antiparasitic agents.[2]
THF
THF, -78°C
SeMe
SeMe
- 78°C
7
8
2
R1
R2
R3
Entry
Product
2a
Yield
Me
Me
Me
Me
70 %
73 %
80 %
1
2
3
We were therefore rather surprised by
a recent paper from
Me
t -Bu
2b
Livinghouse[3a] which described the transformation of 2a to 3a as a
novel reaction, and quoted only one of our previous references in the
field of allyl selenides, neglecting to mention our more recent
publications.[1,4] In order to emphasize our previous contributions to
this area we would now like to describe some of our new results.
i -Pr
i -Pr
Me
Ph
i -Pr
Ph
2c
Me
Ph
2d
2e
77 %
70 %
4
5
Ph
Although the synthesis of allylselenide 2a can be easily achieved from
sodium methylselenolate (from (MeSe)2 and NaH, DMF, 20°C, 75%)
and commercially available, but rather expensive, 3-chloro-2-
SiMe3
Li
SiMe3
Cl
SiMe3
SeMe
MeSeNa
n-BuLi
DMF
20 ºC
THF
- 78°C
(90%)
1a
2a
3a
OEt
OEt
Me3SiOTfcat
O
O
PhS
OSiMe3
SiMe3
1.
PhSO2
O
1. 3a
2. Me3SiCl
O
PhS
H
2. PhSeSePh /H2O2
(50%)
Et3N
(76%)
4
5
6
Scheme 1

1220
LETTERS
SYNLETT
The remaining C-Se bond of the selenopropenes 2 is efficiently cleaved
in THF at -78°C upon reaction with n-butyllithium. The intermediate 3-
lithio-2-[silylmethyl]propenes 3 have been quenched with a variety of
electrophiles, affording the desired adducts in high yields, as shown in
afforded the homoallylic alcohols 10 in excellent overall yields (Table
3).
Table 3 . Condensation of 3 with benzaldehyde
Tables
2 and 3. As can be seen from Table 2, 3-lithio-2-
R1
R2
R1
R2
R1
R2
[trimethylsilylmethyl]propene 3a has been reacted with a range of
aldehydes and ketones, including those with α,β-unsaturation, as well as
with epoxides. The silyl-functionalized unsaturated alcohols 9a-9h have
been obtained in good to excellent yields. Interestingly, enones were
found to undergo exclusive 1,2-addition. No Michael-type products
could be detected using the in situ generated allyllithium 3a. Finally,
condensation between sulfide 4 and reagent 3a proceeded smoothly,
affording the desired silylether 5 in excellent overall yield (Scheme 1).
It is important to note that this transformation can not be effected
successfully with a range of other organometallic derivatives akin to 3a,
thus demonstrating the synthetic value of allyllithium species such as 3.
Si
Li
Si
Si
PhCHO
-78°C
n-BuLi
R3
OH
R3
R3
THF
SeMe
-78°C
Ph
2
3
10
R1
R2
R3
Yield (a)
Entry
Product
Me
Me
Si
Me
Me
t -Bu
Bu-t
OH
10a
87 %
1
Ph
Me
Me
Table 2 .
Condensation of 3a with various electrophiles
Si
Ph
OH
Me
Ph
Me
Ph
Ph
Ph
72 %
82 %
2
3
10b
10c
SiMe3
Li
SiMe3
E
SiMe3
SeMe
2a
E–X
n-BuLi
- 78°C
Ph
THF
- 78°C
3a
Product
SiMe3
9
SiPh3
OH
Ph
Entry
1
Yield(a)
E–X
OH
PhCHO
O
9a
9b
9c
70 %
Si(i-Pr)3
Ph
i-Pr
i-Pr
i-Pr
10d
80 %
4
OH
Ph
SiMe3
OH
2
3
66%
H
(a) All yields are for pure, isolated products
SiMe3
OH
O
78 %
Ph
H
It is worth noting that, in some cases, the direct transformation of bis-
selenide 7 into either 9 or 10 could be realized in a single operation by
the sequential addition of the previous reagents. Such a one-pot
procedure results in increased overall yields compared to the two-step
protocol (Scheme 2).
Ph
SiMe3
OH
H
TIPSO
4
5
6
7
8
9d
9e
9f
41 %
O
O
OTIPS
SiMe3
OH
1. n-BuLi / THF / -78°C
73 % (b)
87 % (b)
79 %
SeMe
SeMe
SiMe3
2. ClSiMe3 / THF / -78°C
OH
R
SiMe3
OH
3. n-BuLi / THF / -78°C
4. RCHO / THF / -78°C
O
O
9
7
R = Ph (65%); R = C3H7 (63%); R = CH2CH2SPh (71%)
SiMe3
9g
Scheme 2
HO
Our results compare most favorably with alternative routes previously
reported in the literature. For example, compound 9a (Table 2, entry 1)
has already been prepared by the thermally induced condensation of 3-
tributylstannyl-2-(trimethylsilylmethyl)propene with benzaldehyde
(150°C, 24h, 61%).[6] The same reaction can be performed at much
lower temperature, promoted by triethylaluminium (Et3Al, -78 to 0°C,
42%).[5] The reaction between the allylstannane, generated in situ from
3-iodo-2-trimethylsilylpropene and SnF2, and polycarbonyl compounds
has been also reported.[7]
SiMe3
OH
O
9h
80 %
H
H
(a) All yields are for pure, isolated compounds. (b) Only the 1,2-adduct is formed
Furthermore, allylsilanes possessing different substituents on the silicon
atom also underwent smooth metallation with n-BuLi to generate the
corresponding allyllithium reagents 3. Trapping with benzaldehyde

November 1998
SYNLETT
1221
3-Chloro-2-[trimethylsilylmethyl]propene 1a is also
a
potential
Acknowledgements: IEM is grateful to the Université catholique de
Louvain, the Actions de recherche concertées - convention 96/01-197
and to Glaxo Wellcome for their financial support (fellowship for F.M.).
precursor of 3a. Condensation of 1a with cyclohexanone can be effected
using lithium naphthalenide under Barbier-type conditions.[8] However,
the authors reported[8] that the synthesis of 3a could not be
accomplished if cyclohexanone was omitted as the allylic reagent
readily dimerized under these conditions. The use of selenium now
References and Notes
[1] (a) Markó, I. E.; Bailey, M.; Murphy, F.; Declercq, J.-P.; Tinant,
B.; Feneau-Dupont, J.; Krief, A.; Dumont, W. Synlett 1995, 123.
(b) Markó, I. E.; Mekhalfia, A.; Bayston, D. J.; Bailey, M.;
Janousek, Z.; Dolan, S. Pure Appl. Chem. 1997, 69, 565.
allows the efficient synthesis of
a whole series of 3-lithio-2-
[silylmethyl]propenes 3 and their further use in synthesis. It is
interesting to note that 3-chloro-2-[trimethylsilylmethyl]propene 1a has
been widely used in organic synthesis but most of the reactions
described so far involve the substitution of either the allylsilane
moiety[9] or the halogen atom thereby introducing this four-carbon unit
as an electrophilic species.[9,10,11,12]
[2] (a) Markó, I. E.; Bayston, D. J.; Mekhalfia, A.; Adams, H. Bull.
Soc. Chim. Belg. 1993, 102, 655. (b) Markó, I. E.; Mekhalfia, A.
Tetrahedron Lett. 1992, 33, 1799. (c) Markó, I. E.; Mechalfia, A.;
Bayston, D. J.; Adams, H. J. Org. Chem. 1992, 57, 2211.
Our preparation of bis-selenide 7 from the corresponding dichloride and
sodium methylselenolate (2 equiv., DMF) obviously implies the
intermediate formation of 3-chloro-2-[methylselenomethyl]propene 11.
This monosubstitution product is isolated in good yield upon reaction of
the dichloride 8 with methylselenol and potassium hydroxide in
THF.[4b] We felt that 11 could also be a valuable precursor to a series of
related heterosubstituted propenes 12 and their subsequent condensation
products 13 (Table 4).[8]
[3] (a) Ryter, K.; Livinghouse, T. J. Org. Chem. 1997, 62, 4842. (b)
Chandrasekhar, S.; Latour, S.; Wuest, J. D.; Zacharie, B. J. Org.
Chem. 1983, 48, 3810. (c) Keck, G. E.; Palani, A. Tetrahedron
Lett. 1993, 34, 3223. (d) Sano, H.; Okawara, M.; Ueno, Y.
Synthesis 1984, 933.
[4] (a) Krief, A.; Derouane, D.; Dumont, W. Synlett 1992, 907. (b)
Krief, A.; Dumont, W. Tetrahedron Lett. 1997, 38, 657.
[5] All yields refer to pure, homogeneous compounds which were
fully characterised by spectroscopic and analytic techniques.
Typical spectroscopic data are:
Table 4 . Synthesis and Condensation of Allylselenides 12
Compound 2: 1H NMR (200 MHz; CDCl3), δ (ppm) 1.65
(CH2Si), 3.06 (CH2Se), 4.5-4.6 (C=CH2). 13C NMR (50 MHz,
CDCl3), δ (ppm) 24.8 (CH2Si), 33.1 (CH2Se), 110 (C=CH2), 143
(C=CH2).
Nu
Cl
Nu
NuNa
1. n-BuLi, THF, -78°C
OH
Ph
DMF
20°C
2. PhCHO, -78°C
3. aq. NaHCO3
SeMe
SeMe
Compound 9; 1H NMR (200 MHz; CDCl3), δ (ppm) 1.4-1.5
(CH2Si), 2.0 (CH2CHOH), 2.85 (CHOH), 4.6 (C=CH2). 13C
11
12
13
Nu
Yield of 13
Entry
Yield of 12
NMR (50 MHz, CDCl3),
δ
(ppm) 26.5 (CH2Si), 46.4
(CH2CHOH), 67.3 (CHOH), 110 (C=CH2), 144 (C=CH2).
[6] Majetich, G.; Nishidie, H.; Zhang, Y. J. Chem. Soc., Perkin
Trans. I 1995, 453.
1
2
3
MeO
80%
60%
92%
12a
12b
12c
90%
13a
13b
13c
[7] (a) Molander, G. A.; Shubert, D. C. J. Am. Chem. Soc. 1986, 108,
4683. (b) Molander, G. A.; Shubert, D. C. J. Am. Chem. Soc.
1987, 109, 6877.
O
N
60%
81%
EtS
[8] Ramon, D. J.; Yus, M. T. Tetrahedron 1993, 49, 10103.
[9] (a) D'aniello, F.; Taddei, M. J. Org. Chem. 1992, 57, 5247. (b)
D'aniello, F.; Matti, D.; Taddei, M. Synlett 1993, 119. (c) Knapp,
S.; O'Connor, U.; Mobilio, D. Tetrahedron Lett. 1980, 21, 4557.
Reaction of allylselenide 11 with O-, N- and S-nucleophiles smoothly
afforded range of 3-methylseleno-2-[heterosubstituted-
[10] Guiles, J. W.; Meyers, A. I. J. Org. Chem. 1991, 56, 6873.
a
methyl]propenes 12 (Table 4). All these derivatives reacted readily with
n-butyllithium (1 equiv.) to produce the corresponding homoallylic
alcohols 13 in good to excellent yield upon quenching with
benzaldehyde.[11,12]
[11] For selected work on polar 3-metallo-2-[heterosubstituted-
methyl]propenes: (a) Gomez, C.; Ramon, D. J.; Yus, M.
Tetrahedron 1993, 49, 4117. (b) Alonso, F.; Lorenzo, E.; Yus, M.
Tetrahedron Lett. 1998, 39, 3303. (c) Vanderheide, T. A. J.; van
der Baan, J. L.; Bickelhaupt, F.; Klumpp, G. W. Tetrahedron Lett.
1992, 33, 475. (d) van der Louw, J.; van der Baan, J. L.; Stichter,
H.; Out, G. J. J.; Dekanter, F. J. J.; Bickelhaupt, F.; Klumpp, G.
W. Tetrahedron 1992, 48, 9877. (e) van der Louw, J.; van der
Baan, J. L.; Out, G. J. J.; Dekanter, F. J. J.; Bickelhaupt, F.;
Klumpp, G. W. Tetrahedron 1992, 48, 9901.
In summary, we have shown that readily available 3-methylseleno-2-
[methylselenomethyl]propene 7 is a useful precursor to a variety of
silylsubstituted allyllithium reagents. These can be efficiently reacted
with a range of electrophiles to afford the corresponding adducts with
excellent chemoselectivity and high yields. Further work is directed
towards broadening the scope of these useful reactions and using allyl
selenides 2 as precursors of the corresponding radicals by cleavage of
their C-Se bond. Full experimental details including further reactions of
these interesting intermediates will be reported in a forthcoming
publication.
[12] For
other
work
on
3-metallo-2-[heterosubstituted-
methyl]propenes (a) Vlaar, C. P.; Klumpp, G. W. Tetrahedron
Lett. 1993, 34, 4651. (b) Trost, B. M. Angew. Chem., Int. Engl.
Ed. 1986, 25, 1.
General procedure for the preparation of allylsilanes from 3-
silyl-2-(methylselenomethyl)prop-1-ene
compounds or epoxides.
2
and carbonyl
n-Butyllithium (1.6 N in hexanes, 1.25 ml, 2 mmol) was slowly

1222
LETTERS
SYNLETT
added to
a
cooled (-78°C) solution of the 3-silyl-2-
combined organic extracts were washed with water (2 x 5 ml) and
dried (MgSO4). The solvents were removed under reduced
pressure to afford a crude mixture which was further purified by
chromatography on buffered (pH 7) silica gel (eluant: pentane/
ether: 9:1) to give the pure adducts 9. Yields are quoted in Table
2.
(methylselenomethyl)prop-1-ene (2 mmol) 2 in anhydrous THF (3
ml) under argon. The resulting yellow solution was stirred for 0.5
h at -78°C and then quenched by slow addition of a solution of the
electrophile in anhydrous THF (2 ml). The mixture was stirred for
0.5 h at -78°C and then treated with a saturated aqueous sodium
bicarbonate solution (2 ml). The mixture was allowed to warm to
room temperature and extracted with ether (3 x 20 ml). The
Note: the TIPS derivative 9d is especially sensitive to traces of
acid leading to unidentified decomposition products.